Project acronym NewSpindleForce
Project A new class of microtubules in the spindle exerting forces on kinetochores
Researcher (PI) Iva Marija Tolic
Host Institution (HI) RUDER BOSKOVIC INSTITUTE
Call Details Consolidator Grant (CoG), LS3, ERC-2014-CoG
Summary At the onset of division the cell forms a spindle, a micro-machine made of microtubules, which divide the chromosomes by pulling on kinetochores, protein complexes on the chromosome. The central question in the field is how accurate chromosome segregation results from the interactions between kinetochores, microtubules and the associated proteins. According to the current paradigm, the forces on kinetochores are produced by k-fibers, bundles of microtubules extending between the spindle pole and the kinetochore. The proposed project is built upon a groundbreaking hypothesis that a new class of microtubules, which we term bridging microtubules, bridge sister kinetochores. Our preliminary results show that bridging microtubules are responsible for the positioning of kinetochores in HeLa and PtK1 cells. Bridging microtubules have not been studied before because this requires cutting-edge microscopy and laser microsurgery techniques. By applying these methods, with which I have extensive expertise, we will determine the organization of these microtubules, identify the proteins that link them with k-fibers, and uncover where and how the forces for kinetochore positioning and movement are generated. My strength is in taking an interdisciplinary approach, which I will use in this project by combining laser microsurgery with genetic perturbations, quantitative measurements of the responses and comparison with theoretical models. Understanding the role of bridging microtubules in force generation and chromosome movements will not only shed light on the mechanism of chromosome segregation, but may also increase the potential of mitotic anticancer strategies, as the spindle is a major target for chemotherapy. The proposed ERC funding is essential for the success of these timely and ambitious experiments, allowing me to strengthen my position as an international leader in research on cell division, thereby increasing Europe's foremost position in this field.
Summary
At the onset of division the cell forms a spindle, a micro-machine made of microtubules, which divide the chromosomes by pulling on kinetochores, protein complexes on the chromosome. The central question in the field is how accurate chromosome segregation results from the interactions between kinetochores, microtubules and the associated proteins. According to the current paradigm, the forces on kinetochores are produced by k-fibers, bundles of microtubules extending between the spindle pole and the kinetochore. The proposed project is built upon a groundbreaking hypothesis that a new class of microtubules, which we term bridging microtubules, bridge sister kinetochores. Our preliminary results show that bridging microtubules are responsible for the positioning of kinetochores in HeLa and PtK1 cells. Bridging microtubules have not been studied before because this requires cutting-edge microscopy and laser microsurgery techniques. By applying these methods, with which I have extensive expertise, we will determine the organization of these microtubules, identify the proteins that link them with k-fibers, and uncover where and how the forces for kinetochore positioning and movement are generated. My strength is in taking an interdisciplinary approach, which I will use in this project by combining laser microsurgery with genetic perturbations, quantitative measurements of the responses and comparison with theoretical models. Understanding the role of bridging microtubules in force generation and chromosome movements will not only shed light on the mechanism of chromosome segregation, but may also increase the potential of mitotic anticancer strategies, as the spindle is a major target for chemotherapy. The proposed ERC funding is essential for the success of these timely and ambitious experiments, allowing me to strengthen my position as an international leader in research on cell division, thereby increasing Europe's foremost position in this field.
Max ERC Funding
2 150 000 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym NMST
Project New methods and interacions in Singularity Theory and beyond
Researcher (PI) Javier Jose Fernandez De Bobadilla De Olazabal
Host Institution (HI) BCAM - BASQUE CENTER FOR APPLIED MATHEMATICS
Call Details Consolidator Grant (CoG), PE1, ERC-2013-CoG
Summary "This project is centred in Singularity Theory and its interactions and applications to Complex and Algebraic Geometry, Differential/symplectic/Contact Topology, Hodge Theory and Algebraic Topology. This subject is still at the core of various developments (Mori's Theory, Symplectic and Contact Geometry, algebro-geometric Donaldson-Thomas Theory, Hodge Theory and D-modules,...) In the present project we propose several directions of development in singularity theory, designed in order to approach the solution of several classical conjectures, and explore new interactions with the latest developments in nearby areas. New problems and conjectures are formulated, which are interesting bottlenecks whose solution would open new development perspectives in the theory, and whose study will need significantly new ideas. We have taken care of finding feasible starting points and interesting classes of singularities where the initial development is less steep. And to find links among the seemingly difernt techniques and problems which we propose.
We deal with the following specific topics: vanishing cohomology of isolated and non-isolated singularities. Rational homotopy generalisations of Hodge Theory and rational vanishing homotopy. Applications to Equisingularity questions. Disentanglement theory and its relation with vanishing homology and homotopy. Symplectic and contact geometry of milnor fibrations. A vast programme in topological equisingularity including a multifaceted attack to Lê-Ramanujan problem. Generalisations of McKay correspondence. Banagl Intersection spaces. Topological and analytic invariants of normal surface singularities. Arc spaces and Nash correspondence. Compactified Jacobians."
Summary
"This project is centred in Singularity Theory and its interactions and applications to Complex and Algebraic Geometry, Differential/symplectic/Contact Topology, Hodge Theory and Algebraic Topology. This subject is still at the core of various developments (Mori's Theory, Symplectic and Contact Geometry, algebro-geometric Donaldson-Thomas Theory, Hodge Theory and D-modules,...) In the present project we propose several directions of development in singularity theory, designed in order to approach the solution of several classical conjectures, and explore new interactions with the latest developments in nearby areas. New problems and conjectures are formulated, which are interesting bottlenecks whose solution would open new development perspectives in the theory, and whose study will need significantly new ideas. We have taken care of finding feasible starting points and interesting classes of singularities where the initial development is less steep. And to find links among the seemingly difernt techniques and problems which we propose.
We deal with the following specific topics: vanishing cohomology of isolated and non-isolated singularities. Rational homotopy generalisations of Hodge Theory and rational vanishing homotopy. Applications to Equisingularity questions. Disentanglement theory and its relation with vanishing homology and homotopy. Symplectic and contact geometry of milnor fibrations. A vast programme in topological equisingularity including a multifaceted attack to Lê-Ramanujan problem. Generalisations of McKay correspondence. Banagl Intersection spaces. Topological and analytic invariants of normal surface singularities. Arc spaces and Nash correspondence. Compactified Jacobians."
Max ERC Funding
1 140 601 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym OPTOMOT
Project Optical dissection of cortical motor circuits
Researcher (PI) Daniel Andreas Huber
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Consolidator Grant (CoG), LS5, ERC-2013-CoG
Summary "The motor cortex plays a key role in learning and orchestrating fine voluntary movements, which dominate many aspects of our daily lives.
Despite decades of research, considerable controversy remains over the functional organization of this forebrain area and its role in goal directed action. In this project we will combine cutting edge in vivo two-photon imaging, decoding methods and optogenetic manipulations to study different motor related circuits with single cell resolution. This approach will provide us, literally, unprecedented insights into the activity dynamics of large cortical networks during goal directed action. We expect that these experiments in rodents will not only help us understand some of the basic neuronal circuit mechanisms that govern our own actions, but they can potentially pave the way towards more targeted strategies for neuroprosthetic devices."
Summary
"The motor cortex plays a key role in learning and orchestrating fine voluntary movements, which dominate many aspects of our daily lives.
Despite decades of research, considerable controversy remains over the functional organization of this forebrain area and its role in goal directed action. In this project we will combine cutting edge in vivo two-photon imaging, decoding methods and optogenetic manipulations to study different motor related circuits with single cell resolution. This approach will provide us, literally, unprecedented insights into the activity dynamics of large cortical networks during goal directed action. We expect that these experiments in rodents will not only help us understand some of the basic neuronal circuit mechanisms that govern our own actions, but they can potentially pave the way towards more targeted strategies for neuroprosthetic devices."
Max ERC Funding
1 997 671 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym PALEOCHAR
Project PALEOCHAR: Insights into the Neanderthals and their demise from the study of microscopic and molecular charred matter in Middle Palaeolithic sediments
Researcher (PI) Carolina Mallol Duque
Host Institution (HI) UNIVERSIDAD DE LA LAGUNA
Call Details Consolidator Grant (CoG), SH6, ERC-2014-CoG
Summary Who were the Neanderthals and what caused their demise? To answer these questions, the classic approach in archaeology relies on the analysis of the Neanderthals' stone-tool assemblages and the mineralized bone remains of their dietary intake. Although this approach has yielded a great deal of important information about the Neanderthals’ fate, it is also limited in the sense that the only evidence that is considered is in-organic in nature. In the current proposal, we attempt to answer these questions by considering microscopic and molecular evidence that is organic in nature. By studying the organic sedimentary record at such fine scales, we are able to extract information about, for example, the fat contents of the Neanderthal food, the way they made fire, the arrangements of their living spaces, their surrounding vegetation and the climatic conditions where they lived. By combining these different sources of information we aim to provide a more complete picture of the Neanderthals and the reason of their disappearance.
Specifically, the PALEOCHAR project examines how Neanderthal diet, fire technology, settlement patterns, and surrounding vegetation were affected by changing climatic conditions. To do so, the project will integrate methodologies from micromorphology and organic geochemistry. A key and innovative aspect of the proposal is the consideration of microscopic and molecular evidence that is both organic and charred in nature. Climatic changes and behavioural responses will be examined at two Iberian sites which represent two key points along the Neanderthal time-line. The results of this project will make important contributions to the development of new methods for archaeological research, train a new generation of skilled geoarchaeologists knowledgeable in microstratigraphy and applied chemistry, and yield new insights into the Neanderthals and their demise.
Summary
Who were the Neanderthals and what caused their demise? To answer these questions, the classic approach in archaeology relies on the analysis of the Neanderthals' stone-tool assemblages and the mineralized bone remains of their dietary intake. Although this approach has yielded a great deal of important information about the Neanderthals’ fate, it is also limited in the sense that the only evidence that is considered is in-organic in nature. In the current proposal, we attempt to answer these questions by considering microscopic and molecular evidence that is organic in nature. By studying the organic sedimentary record at such fine scales, we are able to extract information about, for example, the fat contents of the Neanderthal food, the way they made fire, the arrangements of their living spaces, their surrounding vegetation and the climatic conditions where they lived. By combining these different sources of information we aim to provide a more complete picture of the Neanderthals and the reason of their disappearance.
Specifically, the PALEOCHAR project examines how Neanderthal diet, fire technology, settlement patterns, and surrounding vegetation were affected by changing climatic conditions. To do so, the project will integrate methodologies from micromorphology and organic geochemistry. A key and innovative aspect of the proposal is the consideration of microscopic and molecular evidence that is both organic and charred in nature. Climatic changes and behavioural responses will be examined at two Iberian sites which represent two key points along the Neanderthal time-line. The results of this project will make important contributions to the development of new methods for archaeological research, train a new generation of skilled geoarchaeologists knowledgeable in microstratigraphy and applied chemistry, and yield new insights into the Neanderthals and their demise.
Max ERC Funding
1 996 750 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym PALEOPLANT
Project Palaeolithic Plant Use in the Western Mediterranean
Researcher (PI) Lydia Zapata
Host Institution (HI) UNIVERSIDAD DEL PAIS VASCO/ EUSKAL HERRIKO UNIBERTSITATEA
Call Details Consolidator Grant (CoG), SH6, ERC-2013-CoG
Summary This project deals with one of the big gaps of knowledge in prehistory, how plant foods and resources were used by preagrarian societies. Plants have been fundamental for human societies across the planet. However, it is a blank when it comes to archaeological evidence of humans eating and exploiting them during most part of Prehistory. This work aims at changing the meat/hunting centred paradigm of Palaeolithic subsistence by readdressing human plant exploitation through a novel interdisciplinary approach. The main objectives are: 1) To assess wild plant exploitation among Palaeolithic-Epipalaeolithic societies, 2) To appraise resilience and change in Palaeolithic-Epipalaeolithic plant use, and 3) To improve archaeological methodology and fieldwork. The chronology of analysis –from the Late Middle Palaeolithic to the Epipalaeolithic- includes two extremely interesting periods: a) the transition from the middle to the upper Palaeolithic with neanderthal extinction and early presence of modern humans which gives us the opportunity to explore and compare whether these groups exploit plant resources in a different way, and b) the climatic change from the Late Pleistocene to the early Holocene which allows to evaluate how last hunter-gatherers from the region adapt to climatic change and new ecological conditions. The challenge of the work is to obtain archaeological visibility of plant use through and interdisciplinary approach that combines: pollen analysis, the study of plant macroremains including underground storage organs (USOs), micromorphology, analysis of microremains such as phytoliths and starch, ethnobotany and use-wear analyses on tools. The different types of evidence to be analysed come from relevant archaeological sites from Spain, Portugal and Morocco. Because a project at this scale has not been developed before, major scientific developments and impact in archaeological science can be safely expected.
Summary
This project deals with one of the big gaps of knowledge in prehistory, how plant foods and resources were used by preagrarian societies. Plants have been fundamental for human societies across the planet. However, it is a blank when it comes to archaeological evidence of humans eating and exploiting them during most part of Prehistory. This work aims at changing the meat/hunting centred paradigm of Palaeolithic subsistence by readdressing human plant exploitation through a novel interdisciplinary approach. The main objectives are: 1) To assess wild plant exploitation among Palaeolithic-Epipalaeolithic societies, 2) To appraise resilience and change in Palaeolithic-Epipalaeolithic plant use, and 3) To improve archaeological methodology and fieldwork. The chronology of analysis –from the Late Middle Palaeolithic to the Epipalaeolithic- includes two extremely interesting periods: a) the transition from the middle to the upper Palaeolithic with neanderthal extinction and early presence of modern humans which gives us the opportunity to explore and compare whether these groups exploit plant resources in a different way, and b) the climatic change from the Late Pleistocene to the early Holocene which allows to evaluate how last hunter-gatherers from the region adapt to climatic change and new ecological conditions. The challenge of the work is to obtain archaeological visibility of plant use through and interdisciplinary approach that combines: pollen analysis, the study of plant macroremains including underground storage organs (USOs), micromorphology, analysis of microremains such as phytoliths and starch, ethnobotany and use-wear analyses on tools. The different types of evidence to be analysed come from relevant archaeological sites from Spain, Portugal and Morocco. Because a project at this scale has not been developed before, major scientific developments and impact in archaeological science can be safely expected.
Max ERC Funding
384 345 €
Duration
Start date: 2014-07-01, End date: 2015-12-31
Project acronym PerformEast
Project Performance-Art in Eastern Europe (1950-1990): History and Theory
Researcher (PI) Sylvia Monika Sasse
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Consolidator Grant (CoG), SH5, ERC-2013-CoG
Summary The aim of this project is to provide, for the very first time, an overview of the historical and transnational development of performance art (performances, actions, happenings) in Eastern Europe during the dictatorship period. Performance art shall not only be presented as an object of study, but also as a central art genre implicitly and explicitly involved both in the investigation of cultural practices and in the creation of alternative ways of action. The project focuses, for one, on the artistic exploration of totalitarian or real-socialist practices, rituals, and gestures, but also on artistic ways of action developed in the course of underground activity. Eastern European performance art came to life under conditions in which it was from the very start considered as dubious both aesthetically and contentwise. However, tolerance, hindrance, and sometimes even prohibition led to a heightened degree of self-reflection, minimalism, abstraction, and analysis; in other words, to characteristics representative of the specificity of East European performance art between 1950 and 1990.
At the same time, the proposed project is to be understood as an archaeological one, for it sets out to reconstruct correlations and interactions between unofficial artistic production and official cultural practice. Moreover, it aims to make available to a broader public artistic endeavours that until now could not be centred on in research fields like art history, theatre-, and cultural studies in an Eastern European context.
The project will concentrate on the following four research areas:
1. Territorial interrelationships (between the Eastern European countries, between East and West)
2. Specificity of practice in Eastern European performance art (subversive affirmation, minimalism, abstraction)
3. Interrelationships between artistic action and political activism in the underground
4. Self-reflection in Eastern European performance art (self-archivisation, self-commentary)
Summary
The aim of this project is to provide, for the very first time, an overview of the historical and transnational development of performance art (performances, actions, happenings) in Eastern Europe during the dictatorship period. Performance art shall not only be presented as an object of study, but also as a central art genre implicitly and explicitly involved both in the investigation of cultural practices and in the creation of alternative ways of action. The project focuses, for one, on the artistic exploration of totalitarian or real-socialist practices, rituals, and gestures, but also on artistic ways of action developed in the course of underground activity. Eastern European performance art came to life under conditions in which it was from the very start considered as dubious both aesthetically and contentwise. However, tolerance, hindrance, and sometimes even prohibition led to a heightened degree of self-reflection, minimalism, abstraction, and analysis; in other words, to characteristics representative of the specificity of East European performance art between 1950 and 1990.
At the same time, the proposed project is to be understood as an archaeological one, for it sets out to reconstruct correlations and interactions between unofficial artistic production and official cultural practice. Moreover, it aims to make available to a broader public artistic endeavours that until now could not be centred on in research fields like art history, theatre-, and cultural studies in an Eastern European context.
The project will concentrate on the following four research areas:
1. Territorial interrelationships (between the Eastern European countries, between East and West)
2. Specificity of practice in Eastern European performance art (subversive affirmation, minimalism, abstraction)
3. Interrelationships between artistic action and political activism in the underground
4. Self-reflection in Eastern European performance art (self-archivisation, self-commentary)
Max ERC Funding
1 998 302 €
Duration
Start date: 2014-10-01, End date: 2019-09-30
Project acronym PERSISTDEBT
Project Debt and Persistence of Financial Shocks
Researcher (PI) Jose Luis Peydro Alcalde
Host Institution (HI) UNIVERSIDAD POMPEU FABRA
Call Details Consolidator Grant (CoG), SH1, ERC-2014-CoG
Summary In 2007 the US and Europe were overwhelmed by a banking crisis, which was followed by a severe economic recession. Historical studies show that financial crises are followed by periods of substantially stronger contraction of aggregate output and employment than non-financial recessions. Those studies also point out that the best predictor of financial crises is an ex-ante strong credit boom which, after the beginning of the crisis, followed by negative overall credit growth. Lastly, financial crises take a long time until recovering the pre-crisis levels.
Why are the effects of credit shocks so strong and persistent over time? Is this effect explained by costly household deleveraging? What is the effect of household debt on consumption, savings and employment? Are there any benefits of debt in crises? Do some effects of the financial crisis work through a reduction in credit supply to firms and projects with high innovative content and productivity (high overall return, but with high credit and liquidity risk for the lenders)? Or are the cleansing effects in financial crises concentrated on the less productive firms? Can macroprudential policies based on strict control of loan-to-value ratios stop the building up of excessive household debt?
We plan to construct several new datasets to study these issues by merging information from different sources. For some issues, like the analysis of the effect of household debt on consumption and employment, we can take advantage of a natural experiment of randomized allocation of debt among individuals derived from the use of lotteries to allocate the rights to buy housing in Spain. In comparison to the existing literature, we can exploit the exogenous variation generated by these lotteries and some other combination of data (including exhaustive credit data) to obtain causal evidence and quantification on the interaction between debt, systemic risk, crises, and the new macroprudential policy.
Summary
In 2007 the US and Europe were overwhelmed by a banking crisis, which was followed by a severe economic recession. Historical studies show that financial crises are followed by periods of substantially stronger contraction of aggregate output and employment than non-financial recessions. Those studies also point out that the best predictor of financial crises is an ex-ante strong credit boom which, after the beginning of the crisis, followed by negative overall credit growth. Lastly, financial crises take a long time until recovering the pre-crisis levels.
Why are the effects of credit shocks so strong and persistent over time? Is this effect explained by costly household deleveraging? What is the effect of household debt on consumption, savings and employment? Are there any benefits of debt in crises? Do some effects of the financial crisis work through a reduction in credit supply to firms and projects with high innovative content and productivity (high overall return, but with high credit and liquidity risk for the lenders)? Or are the cleansing effects in financial crises concentrated on the less productive firms? Can macroprudential policies based on strict control of loan-to-value ratios stop the building up of excessive household debt?
We plan to construct several new datasets to study these issues by merging information from different sources. For some issues, like the analysis of the effect of household debt on consumption and employment, we can take advantage of a natural experiment of randomized allocation of debt among individuals derived from the use of lotteries to allocate the rights to buy housing in Spain. In comparison to the existing literature, we can exploit the exogenous variation generated by these lotteries and some other combination of data (including exhaustive credit data) to obtain causal evidence and quantification on the interaction between debt, systemic risk, crises, and the new macroprudential policy.
Max ERC Funding
1 308 676 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
Project acronym PHYLOCANCER
Project Phylogeography and somatic evolution of cancer tumor cells
Researcher (PI) David Posada Gonzalez
Host Institution (HI) UNIVERSIDAD DE VIGO
Call Details Consolidator Grant (CoG), LS8, ERC-2013-CoG
Summary "By far, most evolutionary research has focused on the changes that occur in the germline of individuals across generations, within and between species. For different reasons, much less attention has been given to the process of change within the somatic line of a multicellular individual. The formation of cancer tumors due to uncontrolled cell proliferation is one of the most prominent forms of somatic evolution. The evolution of cancer tumors in a body can be likened with the evolution of populations in more or less fragmented habitats. The tumor is usually a expanding population of clonal cells, which may differentiate to a bigger or lesser extent (population structure) and disperse to contiguous (range expansion) or more distant tissues (long distance colonization). During tumor progression, this population of cells is subject to distinct somatic evolutionary processes like mutation, drift, selection or migration, which can act at different points in time and geographical space. Very recently, the discovery of extensive intratumor heterogeneity, together with the rise of single cell genomics, has created an unique opportunity to study the phylogeography of cancer tumor cells. So far evolutionary inferences drawn from cancer genomes have been mostly qualitative. Here we propose to study a thousand single cell genomes from different regions in primary tumors and matched metastases. We will develop and apply state-of-the-art statistical and computational techniques from phylogenetics, phylogeography and population genomics to understand the tempo and mode of evolution of cell lineages within and between cancer tumors. By doing so we aim to construct a robust theoretical and methodological evolutionary framework that can contribute to a better understanding of the process of somatic evolution and shed light into the biology of cancer."
Summary
"By far, most evolutionary research has focused on the changes that occur in the germline of individuals across generations, within and between species. For different reasons, much less attention has been given to the process of change within the somatic line of a multicellular individual. The formation of cancer tumors due to uncontrolled cell proliferation is one of the most prominent forms of somatic evolution. The evolution of cancer tumors in a body can be likened with the evolution of populations in more or less fragmented habitats. The tumor is usually a expanding population of clonal cells, which may differentiate to a bigger or lesser extent (population structure) and disperse to contiguous (range expansion) or more distant tissues (long distance colonization). During tumor progression, this population of cells is subject to distinct somatic evolutionary processes like mutation, drift, selection or migration, which can act at different points in time and geographical space. Very recently, the discovery of extensive intratumor heterogeneity, together with the rise of single cell genomics, has created an unique opportunity to study the phylogeography of cancer tumor cells. So far evolutionary inferences drawn from cancer genomes have been mostly qualitative. Here we propose to study a thousand single cell genomes from different regions in primary tumors and matched metastases. We will develop and apply state-of-the-art statistical and computational techniques from phylogenetics, phylogeography and population genomics to understand the tempo and mode of evolution of cell lineages within and between cancer tumors. By doing so we aim to construct a robust theoretical and methodological evolutionary framework that can contribute to a better understanding of the process of somatic evolution and shed light into the biology of cancer."
Max ERC Funding
1 999 900 €
Duration
Start date: 2014-10-01, End date: 2019-09-30
Project acronym PREMETAZOANEVOLUTION
Project Unravelling the unicellular prehistory of metazoans with functional analyses and single-cell genomics
Researcher (PI) Iñaki Ruiz Trillo
Host Institution (HI) UNIVERSIDAD POMPEU FABRA
Call Details Consolidator Grant (CoG), LS8, ERC-2013-CoG
Summary "How multicellular animals (metazoans) emerged from their single-celled ancestor remains a long-standing evolutionary question. Recent genome data has shown that the unicellular ancestor of metazoans already had a complex gene repertoire for genes involved in cell adhesion, cell signaling and transcriptional regulation, including integrins, cadherins, T-box genes, and protein tyrosine kinases. Thus, besides a few metazoan-specific genes, gene co-option and, probably, an increase in gene regulation played important roles into the origin of Metazoa. However, the lack of genetic tools among metazoan’s closest relatives has so far precluded further investigations at the molecular level. Our recent establishment, for the first time, of transgenesis methodologies in two close unicellular relatives of metazoans (both the ichthyosporean Creolimax fragrantissima and the filasterean Capsaspora owczarzaki), allow us to approach these questions in ways that were not previously possible. Thus, we aim to push forward these two model systems and infer, by cell biology and functional genomics, the ancestral function of those genes key to multicellularity in order to understand how they were co-opted for new multicellular functions. In addition, we will analyze the regulation of the different cell stages and the colony formation (syncitial and aggregative multicellularity) in these two organism by functional genomics and identify when and how the metazoan histone code (an important regulatory layer of gene expression) evolved by analyzing the histone code in these taxa. Finally, to understand the ecology, distribution and adaptation of these unicellular taxa we will obtain the complete genome sequence of uncultured lineages by using single-cell genomics. This research will not only markedly improve our understanding of a major biological question (the origin of metazoan multicellularity) but will also generate new data relevant to a broad range of researchers."
Summary
"How multicellular animals (metazoans) emerged from their single-celled ancestor remains a long-standing evolutionary question. Recent genome data has shown that the unicellular ancestor of metazoans already had a complex gene repertoire for genes involved in cell adhesion, cell signaling and transcriptional regulation, including integrins, cadherins, T-box genes, and protein tyrosine kinases. Thus, besides a few metazoan-specific genes, gene co-option and, probably, an increase in gene regulation played important roles into the origin of Metazoa. However, the lack of genetic tools among metazoan’s closest relatives has so far precluded further investigations at the molecular level. Our recent establishment, for the first time, of transgenesis methodologies in two close unicellular relatives of metazoans (both the ichthyosporean Creolimax fragrantissima and the filasterean Capsaspora owczarzaki), allow us to approach these questions in ways that were not previously possible. Thus, we aim to push forward these two model systems and infer, by cell biology and functional genomics, the ancestral function of those genes key to multicellularity in order to understand how they were co-opted for new multicellular functions. In addition, we will analyze the regulation of the different cell stages and the colony formation (syncitial and aggregative multicellularity) in these two organism by functional genomics and identify when and how the metazoan histone code (an important regulatory layer of gene expression) evolved by analyzing the histone code in these taxa. Finally, to understand the ecology, distribution and adaptation of these unicellular taxa we will obtain the complete genome sequence of uncultured lineages by using single-cell genomics. This research will not only markedly improve our understanding of a major biological question (the origin of metazoan multicellularity) but will also generate new data relevant to a broad range of researchers."
Max ERC Funding
1 967 535 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym PROduCTS
Project Predicting environment-specific biotransformation of chemical contaminants
Researcher (PI) Kathrin Barbara Fenner
Host Institution (HI) EIDGENOESSISCHE ANSTALT FUER WASSERVERSORGUNG ABWASSERREINIGUNG UND GEWAESSERSCHUTZ
Call Details Consolidator Grant (CoG), LS9, ERC-2013-CoG
Summary The ability to predict rates and products of microbial biotransformation for a broad variety of chemical contaminants accurately is essential not only for chemical risk management but also in the context of contaminated site remediation or the development of green chemical alternatives. Existing prediction methods, however, fall short of fulfilling these needs mostly because they base predictions on chemical structure only, disregarding the microbial communities responsible for degradation and their actual metabolic potential as shaped by environmental conditions. The long-term goals of the proposed research are to develop the scientific basis and appropriate modeling algorithms for considering the metabolic potential of environmental microbial communities (i.e., the available pools of catalytic enzymes) in biotransformation prediction. It is proposed that enzyme-catalyzed biotransformation reactions are established as the explicit core elements of biotransformation prediction. The reactions so defined will serve as mechanistic basis to (i) experimentally explore the linkage between microbial community gene expression profiles and their observed potential for contaminant biotransformation, and (ii) use chemometrics and pattern analysis in high-dimensional space to mine environment-specific chemical biotransformation data for probabilities of biotransformation reactions. The resulting novel algorithms for the environment-specific prediction of biotransformation rates and products will be implemented into an existing, publically-accessible biotransformation prediction system (http://www.umbbd.ethz.ch/predict). The proposed research is highly interdisciplinary and will profit from the most recent technological and scientific advances in the fields of analytical chemistry, molecular biology and chemo-/bioinformatics to develop a ground-breaking approach for profiling the capacity of microbial communities for contaminant biotransformation.
Summary
The ability to predict rates and products of microbial biotransformation for a broad variety of chemical contaminants accurately is essential not only for chemical risk management but also in the context of contaminated site remediation or the development of green chemical alternatives. Existing prediction methods, however, fall short of fulfilling these needs mostly because they base predictions on chemical structure only, disregarding the microbial communities responsible for degradation and their actual metabolic potential as shaped by environmental conditions. The long-term goals of the proposed research are to develop the scientific basis and appropriate modeling algorithms for considering the metabolic potential of environmental microbial communities (i.e., the available pools of catalytic enzymes) in biotransformation prediction. It is proposed that enzyme-catalyzed biotransformation reactions are established as the explicit core elements of biotransformation prediction. The reactions so defined will serve as mechanistic basis to (i) experimentally explore the linkage between microbial community gene expression profiles and their observed potential for contaminant biotransformation, and (ii) use chemometrics and pattern analysis in high-dimensional space to mine environment-specific chemical biotransformation data for probabilities of biotransformation reactions. The resulting novel algorithms for the environment-specific prediction of biotransformation rates and products will be implemented into an existing, publically-accessible biotransformation prediction system (http://www.umbbd.ethz.ch/predict). The proposed research is highly interdisciplinary and will profit from the most recent technological and scientific advances in the fields of analytical chemistry, molecular biology and chemo-/bioinformatics to develop a ground-breaking approach for profiling the capacity of microbial communities for contaminant biotransformation.
Max ERC Funding
1 996 352 €
Duration
Start date: 2014-06-01, End date: 2019-05-31