Project acronym Evoland
Project Evolution of regulatory landscapes at multiple timescales
Researcher (PI) Jose Luis GOMEZ-SKARMETA
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Advanced Grant (AdG), LS8, ERC-2016-ADG
Summary Evolution of animal morphology relies on changes in developmental programs that control body plans and organ shape. Such changes are thought to arise form alteration of the expression of functionally conserved developmental genes and their vast downstream networks. Although this hypothesis has a profound impact on the way we view animal evolution, final proof is still lacking. The hypothesis calls for evolution to take place mainly through modifications of cis-regulatory elements (CREs) controlling gene expression. However, these genomic regions are precisely those that we understand the least and, until recently, basic knowledge on how regulatory information is organized in the 3D genome or how to spatio-temporally assign CREs to their target genes was unknown.
The advent of next generation sequencing-based tools has made possible to identify genome-wide CREs and reveal how they are organized in the 3D genome. But this new knowledge has been largely ignored by most hypotheses on the evolution of gene expression, development and animal morphology. These new high-throughput methods have been mainly restricted to selected model organisms, and due to the lack of sequence conservation of CREs across lineages, we still have very limited information about the impact of CREs on animal morphology evolution.
By integrating in a systematic and phylogenetically driven manner the contribution of CREs and their 3D organization to animal morphology at different evolutionary scales, we will for the first time link evolution, regulatory information, genome 3D architecture and morphology. We will apply this strategy to study animal morphology along the evolution of deuterostome body plans, the generation of fin morphological diversity in vertebrates, and the recent phenotypic changes in fish adapted to cave environments.
Our proposal will make ground-breaking advances in our understanding of the global principles underlying the evolution of cis-regulatory DNA and animal form.
Summary
Evolution of animal morphology relies on changes in developmental programs that control body plans and organ shape. Such changes are thought to arise form alteration of the expression of functionally conserved developmental genes and their vast downstream networks. Although this hypothesis has a profound impact on the way we view animal evolution, final proof is still lacking. The hypothesis calls for evolution to take place mainly through modifications of cis-regulatory elements (CREs) controlling gene expression. However, these genomic regions are precisely those that we understand the least and, until recently, basic knowledge on how regulatory information is organized in the 3D genome or how to spatio-temporally assign CREs to their target genes was unknown.
The advent of next generation sequencing-based tools has made possible to identify genome-wide CREs and reveal how they are organized in the 3D genome. But this new knowledge has been largely ignored by most hypotheses on the evolution of gene expression, development and animal morphology. These new high-throughput methods have been mainly restricted to selected model organisms, and due to the lack of sequence conservation of CREs across lineages, we still have very limited information about the impact of CREs on animal morphology evolution.
By integrating in a systematic and phylogenetically driven manner the contribution of CREs and their 3D organization to animal morphology at different evolutionary scales, we will for the first time link evolution, regulatory information, genome 3D architecture and morphology. We will apply this strategy to study animal morphology along the evolution of deuterostome body plans, the generation of fin morphological diversity in vertebrates, and the recent phenotypic changes in fish adapted to cave environments.
Our proposal will make ground-breaking advances in our understanding of the global principles underlying the evolution of cis-regulatory DNA and animal form.
Max ERC Funding
2 499 514 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym EVOLECOCOG
Project The evolutionary ecology of cognition across a heterogeneous landscape
Researcher (PI) John Leo Quinn
Host Institution (HI) UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK
Call Details Consolidator Grant (CoG), LS8, ERC-2013-CoG
Summary "Why do individuals vary in their cognitive abilities? This proposal takes the disciplines of cognition and evolutionary biology into a natural setting to answer this question by investigating a variety of proximate causes and population-level consequences of individual variation in cognitive ability. It represents the first large-scale integrative study of cognitive ability on any wild population. State of the art observational (remote sensing and automated self-administration trials of learning in the wild), chemical (stable isotope analysis of diet), physiological (stress, energetics, immunocompetence), molecular (DNA fingerprinting and metabarcoding) and analytical (reaction norm, quantitative genetic) techniques will be used. The chosen study system, the great tit Parus major, is one of the most widely used in Europe, but uniquely here will consist of 12 subpopulations across deciduous and conifer woodland fragments. The proposal’s broad scope is captured in three objectives: 1) To characterise proximate causes of variation in cognitive (associative/reversal learning; problem solving; brain size) and other traits (the reactive-proactive personality axis; bill morphology), all of which can influence similar ecologically important behaviour. Quantitative genetic, social, parasite-mediated, and physiological causes will be explored. 2) To examine links between these traits, and key behaviours and trade-offs, e.g., space use, niche specialization, predation, parental care and promiscuity; and 3) To examine the consequences of this variation for life histories and fitness. The research team consists of the PI, five early career biologists, and three PhD students, and will collaborate with eight researchers from Europe and further afield. The project will reveal ground-breaking insight into why individuals vary in their cognitive ability. It aims to impact a wide scientific community, to raise public interest in science, and to inform EU biodiversity policy."
Summary
"Why do individuals vary in their cognitive abilities? This proposal takes the disciplines of cognition and evolutionary biology into a natural setting to answer this question by investigating a variety of proximate causes and population-level consequences of individual variation in cognitive ability. It represents the first large-scale integrative study of cognitive ability on any wild population. State of the art observational (remote sensing and automated self-administration trials of learning in the wild), chemical (stable isotope analysis of diet), physiological (stress, energetics, immunocompetence), molecular (DNA fingerprinting and metabarcoding) and analytical (reaction norm, quantitative genetic) techniques will be used. The chosen study system, the great tit Parus major, is one of the most widely used in Europe, but uniquely here will consist of 12 subpopulations across deciduous and conifer woodland fragments. The proposal’s broad scope is captured in three objectives: 1) To characterise proximate causes of variation in cognitive (associative/reversal learning; problem solving; brain size) and other traits (the reactive-proactive personality axis; bill morphology), all of which can influence similar ecologically important behaviour. Quantitative genetic, social, parasite-mediated, and physiological causes will be explored. 2) To examine links between these traits, and key behaviours and trade-offs, e.g., space use, niche specialization, predation, parental care and promiscuity; and 3) To examine the consequences of this variation for life histories and fitness. The research team consists of the PI, five early career biologists, and three PhD students, and will collaborate with eight researchers from Europe and further afield. The project will reveal ground-breaking insight into why individuals vary in their cognitive ability. It aims to impact a wide scientific community, to raise public interest in science, and to inform EU biodiversity policy."
Max ERC Funding
1 993 189 €
Duration
Start date: 2015-03-01, End date: 2020-12-31
Project acronym EVOLNA
Project Evolution of LNA Aptamers
Researcher (PI) Jesper Thagaard Wengel
Host Institution (HI) SYDDANSK UNIVERSITET
Call Details Advanced Grant (AdG), LS9, ERC-2010-AdG_20100317
Summary Aptamers are single-stranded oligonucleotides which are able to target peptides, proteins, small molecules or live cells by virtue of their well-defined three-dimensional shapes. Aptamers are typically generated by evolution of specific sequences against a given target by in vitro evolution using the process known as SELEX. Progress of this field with respect to drug development has so far been hampered by the relative large size and poor biostability of evolved aptamers composed of unmodified nucleotides, necessitating tedious and extensive post-SELEX truncation and modification approaches. LNA (locked nucleic acid) is a prominent nucleotide modification which is in the process of revolutionizing gene silencing and RNA detection. LNA however has never been included in de novo aptamer evolution. EVOLNA is an ambitious but coherent research program with the objective of transforming the field of aptamer technology. The vision is to enable evolution of aptamers that per se possess most of the desired properties, thereby alleviating the need for extensive post-SELEX procedures. This will be realized by combining the unique properties of LNA with innovative methods for LNA aptamer evolution. LNA aptamer technology is envisioned to enable evolution of aptamers displaying maximum chemical diversity, minimum size and high biostability. The developed strategies will be applicable not only towards evolution of therapeutic aptamers, which will be the main subject of this program, but also towards evolution of aptamers for biosensing, diagnostic and imaging applications. The program is at the very frontier of biotechnology research and spans the areas of chemistry, molecular biology and drug research.
Summary
Aptamers are single-stranded oligonucleotides which are able to target peptides, proteins, small molecules or live cells by virtue of their well-defined three-dimensional shapes. Aptamers are typically generated by evolution of specific sequences against a given target by in vitro evolution using the process known as SELEX. Progress of this field with respect to drug development has so far been hampered by the relative large size and poor biostability of evolved aptamers composed of unmodified nucleotides, necessitating tedious and extensive post-SELEX truncation and modification approaches. LNA (locked nucleic acid) is a prominent nucleotide modification which is in the process of revolutionizing gene silencing and RNA detection. LNA however has never been included in de novo aptamer evolution. EVOLNA is an ambitious but coherent research program with the objective of transforming the field of aptamer technology. The vision is to enable evolution of aptamers that per se possess most of the desired properties, thereby alleviating the need for extensive post-SELEX procedures. This will be realized by combining the unique properties of LNA with innovative methods for LNA aptamer evolution. LNA aptamer technology is envisioned to enable evolution of aptamers displaying maximum chemical diversity, minimum size and high biostability. The developed strategies will be applicable not only towards evolution of therapeutic aptamers, which will be the main subject of this program, but also towards evolution of aptamers for biosensing, diagnostic and imaging applications. The program is at the very frontier of biotechnology research and spans the areas of chemistry, molecular biology and drug research.
Max ERC Funding
2 497 720 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym HISTFUNC
Project Macroecological studies of long-term historical constraints on functional diversity and ecosystem functioning across continents
Researcher (PI) Jens-Christian Svenning
Host Institution (HI) AARHUS UNIVERSITET
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary "Earth’s environment is ongoing massive changes with strong impacts on ecosystems and their services to human societies. It is thus crucial to improve understanding of ecosystem functioning and its dynamics under environmental change. I propose to do this by assessing the novel hypothesis that ecosystem functioning is subject to long-term constraints mediated by biodiversity effects and driven by past climate change and other historical factors. If supported, we will have to rethink ecosystem ecology, as traditionally ecosystem functioning is understood as the outcome of contemporary environmental drivers and their interplay with dominant species. I will employ an unconventional macroecological approach to ecosystem ecology to investigate this hypothesis for major organism groups and ecosystems across continents, modeling effects of historical factors such as past climate change. My specific objectives are to assess if and how (1) large-scale patterns in functional diversity of a key producer group, vascular plants, and (2) a key consumer group, mammals, are affected by historical factors; (3) if and how plant and mammal functional diversity are linked, and, if such links exist, how and to what extent they are shaped by historical factors; (4) if and how large-scale patterns in vegetation-related ecosystem functioning are shaped by historical factors; (5) if ecosystem functioning is linked to diversity of plants and mammals, and if such links exist, if they are shaped by historical factors; and finally (6) directly translate my findings into a novel framework for predicting spatiotemporal dynamics of ecosystem functioning that accounts for historical constraints. The project relies on extensive geospatial data now available on ecosystem functioning, species distributions, and functional traits as well as on paleodistributions, phylogenies, paleoclimate, environment, and human impacts, in combination with advanced statistical and mechanistic modeling."
Summary
"Earth’s environment is ongoing massive changes with strong impacts on ecosystems and their services to human societies. It is thus crucial to improve understanding of ecosystem functioning and its dynamics under environmental change. I propose to do this by assessing the novel hypothesis that ecosystem functioning is subject to long-term constraints mediated by biodiversity effects and driven by past climate change and other historical factors. If supported, we will have to rethink ecosystem ecology, as traditionally ecosystem functioning is understood as the outcome of contemporary environmental drivers and their interplay with dominant species. I will employ an unconventional macroecological approach to ecosystem ecology to investigate this hypothesis for major organism groups and ecosystems across continents, modeling effects of historical factors such as past climate change. My specific objectives are to assess if and how (1) large-scale patterns in functional diversity of a key producer group, vascular plants, and (2) a key consumer group, mammals, are affected by historical factors; (3) if and how plant and mammal functional diversity are linked, and, if such links exist, how and to what extent they are shaped by historical factors; (4) if and how large-scale patterns in vegetation-related ecosystem functioning are shaped by historical factors; (5) if ecosystem functioning is linked to diversity of plants and mammals, and if such links exist, if they are shaped by historical factors; and finally (6) directly translate my findings into a novel framework for predicting spatiotemporal dynamics of ecosystem functioning that accounts for historical constraints. The project relies on extensive geospatial data now available on ecosystem functioning, species distributions, and functional traits as well as on paleodistributions, phylogenies, paleoclimate, environment, and human impacts, in combination with advanced statistical and mechanistic modeling."
Max ERC Funding
1 499 930 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym IDRICA
Project Improving Drought Resistance in Crops and Arabidopsis
Researcher (PI) Ana Isabel Caño Delgado
Host Institution (HI) CENTRE DE RECERCA EN AGRIGENOMICA CSIC-IRTA-UAB-UB
Call Details Consolidator Grant (CoG), LS9, ERC-2015-CoG
Summary Drought is the first cause of agricultural losses globally, and represents a major threat to food security. Currently, plant biotechnology stands as the most promising strategy to produce crops capable of producing high yields in fed rain conditions. From the study of whole-plants, the main underlying mechanism for responses to drought stress has been uncovered, and multiple drought resistance genes have been engineered into crops. So far, plants with enhanced drought resistance displayed reduced crop yield, which imposes the search of novel approaches to uncouple drought resistance from plant growth. Our laboratory has recently shown, for the first time, that the receptors of Brassinosteroid hormones use cell-specific pathways to allocate different developmental responses during root growth. In particular, we have found that cell-specific components of the stem cell niche have the ability to control cellular responses to stress to promote stem renewal to ensure root growth. Additionally, we have also found that BR mutants are resistant to drought, together opening an exceptional opportunity to investigate the mechanisms that confer drought resistance with cellular specificity in plants. In this project, we will use Brassinosteroid signaling in the Arabidopsis root to investigate the mechanism for drought stress resistance in plant and to design novel molecules able to confer resistance to the drought stress. Finally, we will translate our research results and tools into Sorghum bicolor (Sorghum), a crop cereal of paramount importance in fed rain regions of the planet. Our research will impact in science, providing new avenues for the study of hormone signaling in plants, and in society, by providing sustainable solutions for enhance crop production in limiting water environments.
Summary
Drought is the first cause of agricultural losses globally, and represents a major threat to food security. Currently, plant biotechnology stands as the most promising strategy to produce crops capable of producing high yields in fed rain conditions. From the study of whole-plants, the main underlying mechanism for responses to drought stress has been uncovered, and multiple drought resistance genes have been engineered into crops. So far, plants with enhanced drought resistance displayed reduced crop yield, which imposes the search of novel approaches to uncouple drought resistance from plant growth. Our laboratory has recently shown, for the first time, that the receptors of Brassinosteroid hormones use cell-specific pathways to allocate different developmental responses during root growth. In particular, we have found that cell-specific components of the stem cell niche have the ability to control cellular responses to stress to promote stem renewal to ensure root growth. Additionally, we have also found that BR mutants are resistant to drought, together opening an exceptional opportunity to investigate the mechanisms that confer drought resistance with cellular specificity in plants. In this project, we will use Brassinosteroid signaling in the Arabidopsis root to investigate the mechanism for drought stress resistance in plant and to design novel molecules able to confer resistance to the drought stress. Finally, we will translate our research results and tools into Sorghum bicolor (Sorghum), a crop cereal of paramount importance in fed rain regions of the planet. Our research will impact in science, providing new avenues for the study of hormone signaling in plants, and in society, by providing sustainable solutions for enhance crop production in limiting water environments.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym INDSTOCH
Project Individual stochasticity and population heterogeneity in plant and animal demography
Researcher (PI) Hal Caswell
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Advanced Grant (AdG), LS8, ERC-2012-ADG_20120314
Summary "Variation among individuals in reproduction, survival, and other demographic traits, is universal. It has two potential sources: heterogeneity (differences among individuals in their vital rates) and individual stochasticity (random differences resulting from the application of the same vital rates to identical individuals). The goal of the proposed research is to incorporate individual stochasticity and heterogeneity into demographic models for plants, animals, and humans. The project has three components: (1) a study of variation in longevity, focusing on perturbation analysis of Markov chain models for mortality, (2) an analysis of the reward structure of populations, to quantify individual stochasticity in reproduction and other properties, and (3) the development of models to incorporate heterogeneity and stochasticity into branching process models and diffusion models. These three topics will be integrated using matrix population models, integrodifference equation models, and Markov chain models for the life cycle."
Summary
"Variation among individuals in reproduction, survival, and other demographic traits, is universal. It has two potential sources: heterogeneity (differences among individuals in their vital rates) and individual stochasticity (random differences resulting from the application of the same vital rates to identical individuals). The goal of the proposed research is to incorporate individual stochasticity and heterogeneity into demographic models for plants, animals, and humans. The project has three components: (1) a study of variation in longevity, focusing on perturbation analysis of Markov chain models for mortality, (2) an analysis of the reward structure of populations, to quantify individual stochasticity in reproduction and other properties, and (3) the development of models to incorporate heterogeneity and stochasticity into branching process models and diffusion models. These three topics will be integrated using matrix population models, integrodifference equation models, and Markov chain models for the life cycle."
Max ERC Funding
1 496 655 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym INVFEST
Project Evolutionary and functional analysis of polymorphic inversions in the human genome
Researcher (PI) Mario Cáceres
Host Institution (HI) UNIVERSITAT AUTONOMA DE BARCELONA
Call Details Starting Grant (StG), LS8, ERC-2009-StG
Summary The last years have seen an extraordinary explosion of studies characterizing genome variation at different levels, and have opened new opportunities in deciphering the genetic basis of phenotypic characteristics and the evolutionary forces involved. One of the major breakthroughs has been the discovery of an unprecedented degree of structural variation in the human genome, including deletions, duplications and inversions. However, the main challenge is to understand the biological significance of these genomic changes. In particular, for many years inversions have been the paradigm of evolutionary biology. Thus, the identification of the whole set of human inversions gives us a unique opportunity to investigate the functional and evolutionary consequences of this type of changes at a large scale. The specific objectives of the project are: (1) Catalogue the precise location of all common polymorphic inversions in the human genome; (2) Determine the population distribution and the evolutionary history of these inversions; (3) Investigate the functional consequences and the effects on gene expression of human inversions; and (4) Assess the effect of inversions on nucleotide variation patterns and the role of natural selection in their maintenance. This project will follow a multidisciplinary approach that combines experimental and bioinformatic analyses and will benefit from the great amount of information on the human genome already available and that will be generated in the next months. The proposed research therefore represents a very appropriate and timely contribution to the study of human structural variation and its role in phenotypic variation and evolution. Furthermore, it will provide additional insights on genome function, gene-expression regulation mechanisms, and the association of genetic changes and particular traits, and promises to stir novel hypothesis for future studies.
Summary
The last years have seen an extraordinary explosion of studies characterizing genome variation at different levels, and have opened new opportunities in deciphering the genetic basis of phenotypic characteristics and the evolutionary forces involved. One of the major breakthroughs has been the discovery of an unprecedented degree of structural variation in the human genome, including deletions, duplications and inversions. However, the main challenge is to understand the biological significance of these genomic changes. In particular, for many years inversions have been the paradigm of evolutionary biology. Thus, the identification of the whole set of human inversions gives us a unique opportunity to investigate the functional and evolutionary consequences of this type of changes at a large scale. The specific objectives of the project are: (1) Catalogue the precise location of all common polymorphic inversions in the human genome; (2) Determine the population distribution and the evolutionary history of these inversions; (3) Investigate the functional consequences and the effects on gene expression of human inversions; and (4) Assess the effect of inversions on nucleotide variation patterns and the role of natural selection in their maintenance. This project will follow a multidisciplinary approach that combines experimental and bioinformatic analyses and will benefit from the great amount of information on the human genome already available and that will be generated in the next months. The proposed research therefore represents a very appropriate and timely contribution to the study of human structural variation and its role in phenotypic variation and evolution. Furthermore, it will provide additional insights on genome function, gene-expression regulation mechanisms, and the association of genetic changes and particular traits, and promises to stir novel hypothesis for future studies.
Max ERC Funding
1 475 377 €
Duration
Start date: 2010-02-01, End date: 2015-10-31
Project acronym IPBSL
Project Science and technology development for in situ detection and cjharacterization of subsurface life on the Iberian Pyritic Belt
Researcher (PI) Ricardo Amils Pibernat
Host Institution (HI) INSTITUTO NACIONAL DE TECNICA AEROESPACIAL ESTEBAN TERRADAS
Call Details Advanced Grant (AdG), LS8, ERC-2009-AdG
Summary Terrestrial subsurface geomicrobiology is a matter of growing interest on many level. From a fundamental point of view, it seeks to determine wheter life can be sustained in the absence of radiation. From an astrobiological point of view, it is an interesting model for early life on Earth, as well as a representation of life as it could occur in other planetary bodies. Río Tinto is an unusual extreme acidic environment, it rises in the core of the Iberian Pyritic Belt (IPB), one of the biggest sulfidic ore deposits in the world. Today it is clear that the extreme characteristics of Ró Tinto are not due to mining activity, but to the chemolithotrophic microorganisms thriving in the high concentration of metal sulfides of the IPB. To explore the hypothesis that a continuous underground reactor of chemolithotrophic microorganisms thriving in the rich sulfidic minerals of the IPB is responsible for the extreme conditions found in the river, we propose a drilling project to detect the subsurface microbial activity, the potential resources to support these microbial communities, and to follow the in situ geomicrobiological evolution in real time. In this project, we propose to explore the Río Tinto at deep-basement regions (200-1000 m) by means of new approaches comprising: i) detection of life and estimation of the microbial diversity at the drilling sites providing an instant picture of the subsurface habitat, and ii) real time monitoring, inside the borehole, of physico-chemical parameters and biological activity generating essential information to recognize matter and energy fluxes. All these procesess are associated to long-term changes in the underground habitats and are not fully understood based on seasonal discontinuous subsurface analysis. To achieve these goals we will analize cores and fluids in the field site using new and poweful tools.
Summary
Terrestrial subsurface geomicrobiology is a matter of growing interest on many level. From a fundamental point of view, it seeks to determine wheter life can be sustained in the absence of radiation. From an astrobiological point of view, it is an interesting model for early life on Earth, as well as a representation of life as it could occur in other planetary bodies. Río Tinto is an unusual extreme acidic environment, it rises in the core of the Iberian Pyritic Belt (IPB), one of the biggest sulfidic ore deposits in the world. Today it is clear that the extreme characteristics of Ró Tinto are not due to mining activity, but to the chemolithotrophic microorganisms thriving in the high concentration of metal sulfides of the IPB. To explore the hypothesis that a continuous underground reactor of chemolithotrophic microorganisms thriving in the rich sulfidic minerals of the IPB is responsible for the extreme conditions found in the river, we propose a drilling project to detect the subsurface microbial activity, the potential resources to support these microbial communities, and to follow the in situ geomicrobiological evolution in real time. In this project, we propose to explore the Río Tinto at deep-basement regions (200-1000 m) by means of new approaches comprising: i) detection of life and estimation of the microbial diversity at the drilling sites providing an instant picture of the subsurface habitat, and ii) real time monitoring, inside the borehole, of physico-chemical parameters and biological activity generating essential information to recognize matter and energy fluxes. All these procesess are associated to long-term changes in the underground habitats and are not fully understood based on seasonal discontinuous subsurface analysis. To achieve these goals we will analize cores and fluids in the field site using new and poweful tools.
Max ERC Funding
3 246 000 €
Duration
Start date: 2010-06-01, End date: 2015-05-31
Project acronym LIGHTDRIVENP450S
Project Light-driven Chemical Synthesis using Cytochrome P450s
Researcher (PI) Birger Lindberg Møller
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Advanced Grant (AdG), LS9, ERC-2012-ADG_20120314
Summary The goal of this proposed research initiative is to engineer chloroplasts into production units for high value bio-active natural products. The first aim is to re-route the biosynthetic pathways for these compounds into the chloroplast and to boost compound formation by optimizing and channeling reducing power from photosystem I into to the energy demanding steps. By these measures we aim to overcome the inherent limitations in plants to channel photosynthetic fixed carbon and reducing power directly into production of desired bioactive natural products. Our production targets are diterpenoids with the anti-cancer drug ingenol-3-angelate and the adenylyl cyclase activator forskolin as the two chosen test compounds. Formation of the complicated hydroxylated core structures of these compounds is catalyzed by diterpenoid synthases and cytochrome P450s. These will be identified and expressed in the chloroplast. The ultimate aim is to construct a single supramolecular enzyme complex effectively using solar energy to produce complex diterpenoids. This will be accomplished by tethering the terpenoid synthases and the key P450 enzymes directly to the photosystem I complex using some of the small membrane spanning subunits of photosystem I as membrane anchors. The experimental systems used will initially be transient expression in tobacco and then move to stably transformed moss (Physcomitrella patens). The production system is built on the “share your parts” principle of synthetic biology and the aim is to construct a modular ‘tool box’ as template for tailoring the synthesis of a whole range of valuable bioactive diterpenoids. Typically, these are difficult to obtain because they are produced in very low amounts in plants difficult to cultivate. The proposal opens up entirely new research horizons and removes current bottlenecks in industrial exploitation. The technology holds the promise of true sustainability as it is driven by solar power and CO2.
Summary
The goal of this proposed research initiative is to engineer chloroplasts into production units for high value bio-active natural products. The first aim is to re-route the biosynthetic pathways for these compounds into the chloroplast and to boost compound formation by optimizing and channeling reducing power from photosystem I into to the energy demanding steps. By these measures we aim to overcome the inherent limitations in plants to channel photosynthetic fixed carbon and reducing power directly into production of desired bioactive natural products. Our production targets are diterpenoids with the anti-cancer drug ingenol-3-angelate and the adenylyl cyclase activator forskolin as the two chosen test compounds. Formation of the complicated hydroxylated core structures of these compounds is catalyzed by diterpenoid synthases and cytochrome P450s. These will be identified and expressed in the chloroplast. The ultimate aim is to construct a single supramolecular enzyme complex effectively using solar energy to produce complex diterpenoids. This will be accomplished by tethering the terpenoid synthases and the key P450 enzymes directly to the photosystem I complex using some of the small membrane spanning subunits of photosystem I as membrane anchors. The experimental systems used will initially be transient expression in tobacco and then move to stably transformed moss (Physcomitrella patens). The production system is built on the “share your parts” principle of synthetic biology and the aim is to construct a modular ‘tool box’ as template for tailoring the synthesis of a whole range of valuable bioactive diterpenoids. Typically, these are difficult to obtain because they are produced in very low amounts in plants difficult to cultivate. The proposal opens up entirely new research horizons and removes current bottlenecks in industrial exploitation. The technology holds the promise of true sustainability as it is driven by solar power and CO2.
Max ERC Funding
2 499 699 €
Duration
Start date: 2013-03-01, End date: 2019-02-28
Project acronym LT-NRBS
Project Lab-in-a-tube and Nanorobotic biosensors
Researcher (PI) Samuel Sánchez Ordóñez
Host Institution (HI) FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA
Call Details Starting Grant (StG), LS9, ERC-2012-StG_20111109
Summary The goal of this project is to develop new types of biosensors based on two different approaches: (i) a new bioanalytic microsystem platform for cell growth, manipulation and analysis using on-chip integrated microtubes and (ii) the use of synthetic self-propelled nanomotors for bioanalytical and biosensing applications. Based on the novel “Lab-in-a-tube” concept, we will design a multifunctional device for the capturing, growth and sensing of single cell behaviours inside “glass” microtubes to be employed for diverse biological applications. We will decorate the walls of the microtubes with proteins from the extracellular matrix enabling the long-term study of cellular changes such as mitosis time, spindle reorientation, DNA damage and cellular differentiation. These microtubes are fabricated by the well-established rolled-up nanotechnology developed in the host institution. Moreover, the multifunctionality of the “Lab-in-a-tube” platform will be extended by integrating different modules into a single microtubular unit, bringing up several applications such as optofluidics(bio)sensors, electrodes for electrochemical control and sensing, and magnetic biodetection.
At the IIN institute in IFW Dresden, we are pioneers on the fabrication of catalytic microjet engines (microbots) and their use for transporting different kinds of objects in vitro into a fluid. The remote controlled motion of these autonomous microbots and the transport of microobjects and cells to specific targets within lab-on-a-chip systems is possible. Their walls can be biofunctionalized with enzymes, antibodies or DNA, the catalytic microbots representing a novel and unique tool for biosensing, environmental and biomedical applications. Our next step is to use biocompatible fuels to propel these microbots with the final aim of transporting and delivering drugs in vivo.The separation of cancer cells, bacteria and other biomaterials to build up new tissues or to replace disease cells are also aimed.
Summary
The goal of this project is to develop new types of biosensors based on two different approaches: (i) a new bioanalytic microsystem platform for cell growth, manipulation and analysis using on-chip integrated microtubes and (ii) the use of synthetic self-propelled nanomotors for bioanalytical and biosensing applications. Based on the novel “Lab-in-a-tube” concept, we will design a multifunctional device for the capturing, growth and sensing of single cell behaviours inside “glass” microtubes to be employed for diverse biological applications. We will decorate the walls of the microtubes with proteins from the extracellular matrix enabling the long-term study of cellular changes such as mitosis time, spindle reorientation, DNA damage and cellular differentiation. These microtubes are fabricated by the well-established rolled-up nanotechnology developed in the host institution. Moreover, the multifunctionality of the “Lab-in-a-tube” platform will be extended by integrating different modules into a single microtubular unit, bringing up several applications such as optofluidics(bio)sensors, electrodes for electrochemical control and sensing, and magnetic biodetection.
At the IIN institute in IFW Dresden, we are pioneers on the fabrication of catalytic microjet engines (microbots) and their use for transporting different kinds of objects in vitro into a fluid. The remote controlled motion of these autonomous microbots and the transport of microobjects and cells to specific targets within lab-on-a-chip systems is possible. Their walls can be biofunctionalized with enzymes, antibodies or DNA, the catalytic microbots representing a novel and unique tool for biosensing, environmental and biomedical applications. Our next step is to use biocompatible fuels to propel these microbots with the final aim of transporting and delivering drugs in vivo.The separation of cancer cells, bacteria and other biomaterials to build up new tissues or to replace disease cells are also aimed.
Max ERC Funding
1 499 880 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
