Project acronym MechanoIMM
Project Mechanical Immunoengineering for Enhanced T-cell Immunotherapy
Researcher (PI) Li TANG
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Starting Grant (StG), LS9, ERC-2018-STG
Summary Cancer immunotherapy harnessing the power of a patient’s immune system to fight cancer is transforming the standard-of-care for cancer. Adoptive cell therapy (ACT), a potent immunotherapy that directly infuses a large number of tumour-reactive T cells into patients, has elicited dramatic clinical responses in leukaemia patients recently. However, solid tumour remains a major challenge as tumour employs a number of strategies to prevent effector T cells reaching the tumour sites and attacking cancer by generating a highly immunosuppressive microenvironment. Current strategies are focused on controlling the immune system or the microenvironment using biochemical immunomodulatory reagents to enhance T cell based immunotherapy. Approaches exploiting biophysical and mechanical cues for immunomodulation are largely underappreciated. In this proposal, we aim to exploit mechanical immunoengineering strategies through biophysical cues to develop novel immune related treatments to enhance the efficacy and safety of adoptive T cell therapy for cancer. We will first develop a mechano-training approach to promote the T cell infiltration into tumour tissues using engineered microfluidic system for controlled force application on T cells in a high through-put manner. Second, we will develop a mechano-responsive nanoparticle delivery system to selectively deliver T-cell-supporting drugs in tumour to overcome the immune suppression in the microenvironment and enhance T cell functions for killing cancer. Third, we will develop mechano-inducible cytokine-secreting T cell therapies to augment the efficacy and minimize the toxicity of ACT by exploiting and targeting the difference in tissue stiffness between tumour and healthy tissues. This proposed project will open a new horizon for immunoengineering through biomechanical modulation of immunity for enhanced cancer immunotherapy and provide insight into the fundamentals of mechanotransduction in immune system in health and disease.
Summary
Cancer immunotherapy harnessing the power of a patient’s immune system to fight cancer is transforming the standard-of-care for cancer. Adoptive cell therapy (ACT), a potent immunotherapy that directly infuses a large number of tumour-reactive T cells into patients, has elicited dramatic clinical responses in leukaemia patients recently. However, solid tumour remains a major challenge as tumour employs a number of strategies to prevent effector T cells reaching the tumour sites and attacking cancer by generating a highly immunosuppressive microenvironment. Current strategies are focused on controlling the immune system or the microenvironment using biochemical immunomodulatory reagents to enhance T cell based immunotherapy. Approaches exploiting biophysical and mechanical cues for immunomodulation are largely underappreciated. In this proposal, we aim to exploit mechanical immunoengineering strategies through biophysical cues to develop novel immune related treatments to enhance the efficacy and safety of adoptive T cell therapy for cancer. We will first develop a mechano-training approach to promote the T cell infiltration into tumour tissues using engineered microfluidic system for controlled force application on T cells in a high through-put manner. Second, we will develop a mechano-responsive nanoparticle delivery system to selectively deliver T-cell-supporting drugs in tumour to overcome the immune suppression in the microenvironment and enhance T cell functions for killing cancer. Third, we will develop mechano-inducible cytokine-secreting T cell therapies to augment the efficacy and minimize the toxicity of ACT by exploiting and targeting the difference in tissue stiffness between tumour and healthy tissues. This proposed project will open a new horizon for immunoengineering through biomechanical modulation of immunity for enhanced cancer immunotherapy and provide insight into the fundamentals of mechanotransduction in immune system in health and disease.
Max ERC Funding
1 499 800 €
Duration
Start date: 2018-12-01, End date: 2023-11-30
Project acronym NANOSYM
Project Symbiotic bacteria as a delivery system for Nanobodies that target the insect-parasite interplay
Researcher (PI) Jan Van Den Abbeele
Host Institution (HI) PRINS LEOPOLD INSTITUUT VOOR TROPISCHE GENEESKUNDE
Call Details Starting Grant (StG), LS9, ERC-2011-StG_20101109
Summary The tsetse fly (Glossina spp.) salivary gland is the final micro-environment where the Trypanosoma brucei parasites adhere and undergo a complex re-programming cycle resulting in an end stage that is re-programmed to continue its life cycle in a new mammalian host. The molecular parasite-vector communications that orchestrate this trypanosome development in tsetse fly salivary glands remain unknown mainly due to the limited availability of experimental tools for functional research. We hypothesize that an innovative paratransgenic approach using the Sodalis glossinidius endosymbiont to deliver Nanobodies that target the trypanosome-tsetse fly crosstalk will open a new avenue to unravel the molecular determinants of this specific parasite-vector association. In this project I will develop an innovative Sodalis-based internal delivery system for Nanobodies to target the tsetse fly – trypanosome interplay and, as final outcome, will generate a trypanosome-resistant tsetse fly. In addition, I will explore the completely ‘unknown’ of the molecular nature of trypanosome adherence to the salivary gland epithelium. This will be addressed by a challenging proteomic-based approach on the tsetse salivary gland - trypanosome membrane complex and by the newly developed paratransgenic approach using the S. glossinidius endosymbiont as an internal delivery system for salivary gland epithelium-targeting Nanobodies. The application of this innovative concept of using pathogen-targeting Nanobodies delivered by insect symbiotic bacteria could be extended to other vector-pathogen systems such as Anopheles gambiae – Plasmodium falciparum and Aedes aegypti – dengue virus.
Summary
The tsetse fly (Glossina spp.) salivary gland is the final micro-environment where the Trypanosoma brucei parasites adhere and undergo a complex re-programming cycle resulting in an end stage that is re-programmed to continue its life cycle in a new mammalian host. The molecular parasite-vector communications that orchestrate this trypanosome development in tsetse fly salivary glands remain unknown mainly due to the limited availability of experimental tools for functional research. We hypothesize that an innovative paratransgenic approach using the Sodalis glossinidius endosymbiont to deliver Nanobodies that target the trypanosome-tsetse fly crosstalk will open a new avenue to unravel the molecular determinants of this specific parasite-vector association. In this project I will develop an innovative Sodalis-based internal delivery system for Nanobodies to target the tsetse fly – trypanosome interplay and, as final outcome, will generate a trypanosome-resistant tsetse fly. In addition, I will explore the completely ‘unknown’ of the molecular nature of trypanosome adherence to the salivary gland epithelium. This will be addressed by a challenging proteomic-based approach on the tsetse salivary gland - trypanosome membrane complex and by the newly developed paratransgenic approach using the S. glossinidius endosymbiont as an internal delivery system for salivary gland epithelium-targeting Nanobodies. The application of this innovative concept of using pathogen-targeting Nanobodies delivered by insect symbiotic bacteria could be extended to other vector-pathogen systems such as Anopheles gambiae – Plasmodium falciparum and Aedes aegypti – dengue virus.
Max ERC Funding
1 444 370 €
Duration
Start date: 2011-11-01, End date: 2016-10-31
Project acronym noMAGIC
Project Noninvasive Manipulation of Gating in Ion Channels
Researcher (PI) ANNA MORONI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI MILANO
Call Details Advanced Grant (AdG), LS9, ERC-2015-AdG
Summary noMAGIC has the visionary goal of engineering genetically encoded ion channels, which can be remotely controlled (gated) by stimuli that penetrate deep into human tissue without negative side effects. The control over ion channel activity by deep penetrating stimuli will revolutionize research in neurobiology and physiology as it paves the way for remote and genuine non-invasive control of cell activity in vivo. Synthetic channels, which can be gated by magnetic fields (MF), near infrared (NIR) radiation or ultrasound (US) will be engineered in the frame of noMAGIC by three complementary work packages (WP1-3). Design and engineering of the channels will be performed in WP1 by reiterated steps of rational and irrational design, high throughput screening and in vitro and in vivo functional testing. We have identified two sensor modules for MF and NIR radiation, respectively, which will be functionally connected to a channel pore for a remote control of gating. For the US-gated channel we will engineer a channel pore that is maximally responding to local changes in the lipid environment induced by US. Design and engineering of channels will be complemented by a computational approach (WP2), which analyses, from elastic network models, the mechanical connections in the channel pore and which extracts information on the forces, which are required to gate a channel by the three stimuli. The outcome of WP2 will provide general design rules for synthetic channels with implications much beyond the present project. WP3 also contributes to the engineering effort in WP1 by a spectrum of avant-garde spectroscopic methods, which resolve structural changes of the channel proteins under the influence of remote stimuli. These structural insights will greatly advance our understanding of structure/function correlates in composite ion channels and it will inspire the design and engineering of channels, which respond to remote stimuli.
Summary
noMAGIC has the visionary goal of engineering genetically encoded ion channels, which can be remotely controlled (gated) by stimuli that penetrate deep into human tissue without negative side effects. The control over ion channel activity by deep penetrating stimuli will revolutionize research in neurobiology and physiology as it paves the way for remote and genuine non-invasive control of cell activity in vivo. Synthetic channels, which can be gated by magnetic fields (MF), near infrared (NIR) radiation or ultrasound (US) will be engineered in the frame of noMAGIC by three complementary work packages (WP1-3). Design and engineering of the channels will be performed in WP1 by reiterated steps of rational and irrational design, high throughput screening and in vitro and in vivo functional testing. We have identified two sensor modules for MF and NIR radiation, respectively, which will be functionally connected to a channel pore for a remote control of gating. For the US-gated channel we will engineer a channel pore that is maximally responding to local changes in the lipid environment induced by US. Design and engineering of channels will be complemented by a computational approach (WP2), which analyses, from elastic network models, the mechanical connections in the channel pore and which extracts information on the forces, which are required to gate a channel by the three stimuli. The outcome of WP2 will provide general design rules for synthetic channels with implications much beyond the present project. WP3 also contributes to the engineering effort in WP1 by a spectrum of avant-garde spectroscopic methods, which resolve structural changes of the channel proteins under the influence of remote stimuli. These structural insights will greatly advance our understanding of structure/function correlates in composite ion channels and it will inspire the design and engineering of channels, which respond to remote stimuli.
Max ERC Funding
2 409 209 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym NOVABREED
Project Novel variation in plant breeding and the plant pan-genomes
Researcher (PI) Michele Morgante
Host Institution (HI) UNIVERSITA DEGLI STUDI DI UDINE
Call Details Advanced Grant (AdG), LS9, ERC-2011-ADG_20110310
Summary "The analysis of variation in plants has revealed that their genomes are characterised by high levels of structural variation, consisting of both smaller insertion/deletions, mostly due to recent insertions of transposable elements, and of larger insertion/deletion similar to those termed in humans Copy Number Variants (CNVs). These observations indicate that a single genome sequence might not reflect the entire genomic complement of a species, and prompted us to introduce the concept of the plant pan-genome, including core genomic features common to all individuals and a Dispensable Genome (DG) composed of partially shared and/or non shared DNA sequence elements. The very active transposable element systems present in many plant genomes may account for a large fraction of the DG. The mechanisms by which the CNV-like variants are generated and the direction of the mutational events are still unknown. Uncovering the intriguing nature of the DG, i.e. its composition, origin and function, represents a step forward towards an understanding of the processes generating genetic diversity and phenotypic variation. Additionally, since the DG clearly appears to be for the most part the youngest and most dynamic component of the pan genome, it is of great interest to understand whether it is a major contributor to the creation of new genetic variation in plant evolution and more specifically in the breeding process. We thus aim at:
i) defining extent and composition of the pan genome in two plant species, maize and grapevine;
ii) identifying the different mechanisms that generate and maintain the dispensable portion in these 2 species;
iii) identifying the phenotypic effects of the DG;
iv) estimating the rates and modes of creation of new genetic variation due to DG components and whether this could represent an important factor in the breeding process;
v) extending our findings to other plant species for which the genome sequence in the meantime may have become available."
Summary
"The analysis of variation in plants has revealed that their genomes are characterised by high levels of structural variation, consisting of both smaller insertion/deletions, mostly due to recent insertions of transposable elements, and of larger insertion/deletion similar to those termed in humans Copy Number Variants (CNVs). These observations indicate that a single genome sequence might not reflect the entire genomic complement of a species, and prompted us to introduce the concept of the plant pan-genome, including core genomic features common to all individuals and a Dispensable Genome (DG) composed of partially shared and/or non shared DNA sequence elements. The very active transposable element systems present in many plant genomes may account for a large fraction of the DG. The mechanisms by which the CNV-like variants are generated and the direction of the mutational events are still unknown. Uncovering the intriguing nature of the DG, i.e. its composition, origin and function, represents a step forward towards an understanding of the processes generating genetic diversity and phenotypic variation. Additionally, since the DG clearly appears to be for the most part the youngest and most dynamic component of the pan genome, it is of great interest to understand whether it is a major contributor to the creation of new genetic variation in plant evolution and more specifically in the breeding process. We thus aim at:
i) defining extent and composition of the pan genome in two plant species, maize and grapevine;
ii) identifying the different mechanisms that generate and maintain the dispensable portion in these 2 species;
iii) identifying the phenotypic effects of the DG;
iv) estimating the rates and modes of creation of new genetic variation due to DG components and whether this could represent an important factor in the breeding process;
v) extending our findings to other plant species for which the genome sequence in the meantime may have become available."
Max ERC Funding
2 473 500 €
Duration
Start date: 2012-07-01, End date: 2017-12-31
Project acronym PASTFORWARD
Project Development trajectories of temperate forest plant communities under global change: combining hindsight and forecasting (PASTFORWARD)
Researcher (PI) Kris Verheyen
Host Institution (HI) UNIVERSITEIT GENT
Call Details Consolidator Grant (CoG), LS9, ERC-2013-CoG
Summary "The last decades are characterized by an upsurge of research on the impacts of global environmental changes on forests. Climate warming, atmospheric deposition of acidifying and eutrophying pollutants and land-use change are three of the most important threats to biodiversity in temperate forests. However, most studies focused on the effects of single factors over short time periods, such that our ability to predict the combined effects of multiple global change drivers over longer time periods remains rudimentary. The lack of knowledge on effects of global change drivers on forest herb layer communities is particularly striking, since the herb layer contains the largest part of vascular plant diversity in temperate forests and provides key ecosystem services. Therefore PASTFORWARD will build an integrative understanding of the interactive effects of land-use change, atmospheric deposition and climate warming on forest herb layer communities, starting from the insight that changes in herb layer communities are driven primarily by past land use, but can be modulated by atmospheric deposition, climate warming and forest management. Indeed, it is still largely ignored that sensible predictions of herb layer development trajectories under global change can only be made by taking the forest’s land-use history into account, as legacies of past land use can leave century-long imprints on forest herb layer communities. Three complementary data sources (a database with resurveyed vegetation plots, field measurements in a pan-European network of resurvey plots, and a multi-factor experiment) combined with an ecosystem model will be used. Furthermore, concepts and tools from different disciplines, ranging from history over sylviculture to community and ecosystem ecology will be applied. The results of PASTFORWARD will help forest managers and policy makers in taking more informed decisions on how to combine resource extraction with biodiversity conservation."
Summary
"The last decades are characterized by an upsurge of research on the impacts of global environmental changes on forests. Climate warming, atmospheric deposition of acidifying and eutrophying pollutants and land-use change are three of the most important threats to biodiversity in temperate forests. However, most studies focused on the effects of single factors over short time periods, such that our ability to predict the combined effects of multiple global change drivers over longer time periods remains rudimentary. The lack of knowledge on effects of global change drivers on forest herb layer communities is particularly striking, since the herb layer contains the largest part of vascular plant diversity in temperate forests and provides key ecosystem services. Therefore PASTFORWARD will build an integrative understanding of the interactive effects of land-use change, atmospheric deposition and climate warming on forest herb layer communities, starting from the insight that changes in herb layer communities are driven primarily by past land use, but can be modulated by atmospheric deposition, climate warming and forest management. Indeed, it is still largely ignored that sensible predictions of herb layer development trajectories under global change can only be made by taking the forest’s land-use history into account, as legacies of past land use can leave century-long imprints on forest herb layer communities. Three complementary data sources (a database with resurveyed vegetation plots, field measurements in a pan-European network of resurvey plots, and a multi-factor experiment) combined with an ecosystem model will be used. Furthermore, concepts and tools from different disciplines, ranging from history over sylviculture to community and ecosystem ecology will be applied. The results of PASTFORWARD will help forest managers and policy makers in taking more informed decisions on how to combine resource extraction with biodiversity conservation."
Max ERC Funding
1 887 780 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym PERVOL
Project Perception of Plant Volatiles
Researcher (PI) Matthias Erb
Host Institution (HI) UNIVERSITAET BERN
Call Details Starting Grant (StG), LS9, ERC-2016-STG
Summary The capacity to produce and perceive organic chemicals is essential for most cellular organisms. Plant leaves that are attacked by insect herbivores for instance start releasing distinct blends of herbivore-induced plant volatiles, which in turn can be perceived by non-attacked tissues. These tissues then respond more rapidly and more strongly to herbivore attack. One major question that constrains the current understanding of plant volatile communication is how plants perceive herbivore induced volatiles. Can plants smell danger by detecting certain volatiles with specific receptors? Or are other mechanisms at play? Answering these questions would push the boundaries of plant signaling research, as it would allow for the creation of perception impaired mutants to perform detailed analyses of the biological functions and potential agricultural benefits of plant volatile perception.
My recent work identified indole as a key herbivore induced volatile priming signal in maize. As indole is produced by many different plant species and has been well studied as a bacterial volatile, it is an ideal candidate to study the mechanisms and biological functions of plant volatile perception. The key objectives of PERVOL are 1) to develop a new high-throughput plant volatile sampling system for genetic screens of indole perception, 2) to use the system to identify molecular mechanisms of indole perception and 3) to create indole perception mutants to uncover novel biological functions of volatile priming. If successful, PERVOL will set technological standards by providing the community with an innovative and powerful volatile sampling system. Furthermore, it will push the field of plant volatile research by elucidating mechanisms of herbivore induced volatile perception, generating new genetic resources for functional investigations of plant volatile signaling and testing new potential biological functions of the perception of herbivore induced volatiles.
Summary
The capacity to produce and perceive organic chemicals is essential for most cellular organisms. Plant leaves that are attacked by insect herbivores for instance start releasing distinct blends of herbivore-induced plant volatiles, which in turn can be perceived by non-attacked tissues. These tissues then respond more rapidly and more strongly to herbivore attack. One major question that constrains the current understanding of plant volatile communication is how plants perceive herbivore induced volatiles. Can plants smell danger by detecting certain volatiles with specific receptors? Or are other mechanisms at play? Answering these questions would push the boundaries of plant signaling research, as it would allow for the creation of perception impaired mutants to perform detailed analyses of the biological functions and potential agricultural benefits of plant volatile perception.
My recent work identified indole as a key herbivore induced volatile priming signal in maize. As indole is produced by many different plant species and has been well studied as a bacterial volatile, it is an ideal candidate to study the mechanisms and biological functions of plant volatile perception. The key objectives of PERVOL are 1) to develop a new high-throughput plant volatile sampling system for genetic screens of indole perception, 2) to use the system to identify molecular mechanisms of indole perception and 3) to create indole perception mutants to uncover novel biological functions of volatile priming. If successful, PERVOL will set technological standards by providing the community with an innovative and powerful volatile sampling system. Furthermore, it will push the field of plant volatile research by elucidating mechanisms of herbivore induced volatile perception, generating new genetic resources for functional investigations of plant volatile signaling and testing new potential biological functions of the perception of herbivore induced volatiles.
Max ERC Funding
1 989 938 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym POLYADAPT
Project Molecular-genetic mechanisms of extreme adaptation in a polyphagous agricultural pest
Researcher (PI) Thomas Bert VAN LEEUWEN
Host Institution (HI) UNIVERSITEIT GENT
Call Details Consolidator Grant (CoG), LS9, ERC-2017-COG
Summary Generalist (polyphagous) herbivores can feed and reproduce on many different plant species and include some of the most pesticide resistant and notorious pests in agriculture. An evolutionary link between host plant range and the development of pesticide resistance has been suggested. Although crucial for devising efficient crop protection strategies, the mechanisms underlying rapid adaptation are not well understood, especially in generalists. The spider mite Tetranychus urticae is a global pest known to feed on 1,100 different hosts from 140 plant families, including most major crops. With experimental advances and new tools developed for T. urticae, we are now poised for fundamental advances in understanding the molecular genetic make-up of adaption in generalist pests. We will generate a large collection of fully inbred and resistant mite strains and describe the sampled genomic variation in the context of selection and adaptation. We will study gene regulation mechanisms and quantify cis versus trans regulation of gene expression on a genome wide scale. We will then create a unique population resource that will allow us to map master regulators of gene expression and construct a gene-regulatory network of adaptation responsive genes. In a highly replicated experimental evolution study, combined with Bulk Segregant Analysis (BSA), we will uncover, without a prior hypothesis, the genomic loci that underlie complex cases of resistance and plant adaptation. A core set of adaptation genes will be validated by functional expression and high-throughput interaction assays. Further validation will come from the development of genome editing tools. In summary, POLYADAPT will exploit the genomic tools now available for spider mites to elucidate regulatory and causal variants underlying the extreme adaptation potential of polyphagous pests. This will in the long term lead to innovative methods of pest management.
Summary
Generalist (polyphagous) herbivores can feed and reproduce on many different plant species and include some of the most pesticide resistant and notorious pests in agriculture. An evolutionary link between host plant range and the development of pesticide resistance has been suggested. Although crucial for devising efficient crop protection strategies, the mechanisms underlying rapid adaptation are not well understood, especially in generalists. The spider mite Tetranychus urticae is a global pest known to feed on 1,100 different hosts from 140 plant families, including most major crops. With experimental advances and new tools developed for T. urticae, we are now poised for fundamental advances in understanding the molecular genetic make-up of adaption in generalist pests. We will generate a large collection of fully inbred and resistant mite strains and describe the sampled genomic variation in the context of selection and adaptation. We will study gene regulation mechanisms and quantify cis versus trans regulation of gene expression on a genome wide scale. We will then create a unique population resource that will allow us to map master regulators of gene expression and construct a gene-regulatory network of adaptation responsive genes. In a highly replicated experimental evolution study, combined with Bulk Segregant Analysis (BSA), we will uncover, without a prior hypothesis, the genomic loci that underlie complex cases of resistance and plant adaptation. A core set of adaptation genes will be validated by functional expression and high-throughput interaction assays. Further validation will come from the development of genome editing tools. In summary, POLYADAPT will exploit the genomic tools now available for spider mites to elucidate regulatory and causal variants underlying the extreme adaptation potential of polyphagous pests. This will in the long term lead to innovative methods of pest management.
Max ERC Funding
1 926 250 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym POPFULL
Project System analysis of a bio-energy plantation: full greenhouse gas balance and energy accounting
Researcher (PI) Reinhart J.M. Ceulemans
Host Institution (HI) UNIVERSITEIT ANTWERPEN
Call Details Advanced Grant (AdG), LS9, ERC-2008-AdG
Summary One of the strategies for mitigation of anthropogenic greenhouse gas emissions that is receiving a lot of attention in this post-Kyoto era, is the use of bio-energy as a replacement for fossil fuels. Among the different alternatives of bio-energy production the use of biomass crops such as fast-growing woody crops under short rotation coppice (SRC) regimes - is probably the most suited, in particular in the EU. Two issues need to be addressed before the efficacy of bio-energy for carbon mitigation can be conclusively assessed, i.e. (i) a full life cycle analysis (LCA) of the global warming contribution of SRC, and (ii) and an assessment of the energy efficiency of the system. The objectives of this project are: (i) to make a full LCA balance of the most important greenhouse gases (CO2, CH4, N2O, H2O and O3) and of the volatile organic compounds (VOC s), and (ii) to make a full energy accounting of a SRC plantation with fast-growing trees. The project will involve both an experimental approach at a representative field site in Belgium and a modelling part. For the experimental approach a SRC of poplar (Populus) will be monitored during the course of 1+3 years, harvested and transformed into bio-energy. Eddy covariance techniques will be used to monitor net fluxes of all greenhouse gases and VOC's, in combination with common assessments of biomass pools (incl. soil) and fluxes. For the energy accounting we will use life cycle analysis and energy efficiency assessments over the entire life cycle of the SRC plantation until the production of electricity and heat. A significant process based modeling component will integrate the collected knowledge on the greenhouse gas and energy balances toward predictions and simulations of the net reduction of fossil greenhouse gas emissions (avoided emissions) of SRC over different rotation cycles, global warming scenarios, and management strategies.
Summary
One of the strategies for mitigation of anthropogenic greenhouse gas emissions that is receiving a lot of attention in this post-Kyoto era, is the use of bio-energy as a replacement for fossil fuels. Among the different alternatives of bio-energy production the use of biomass crops such as fast-growing woody crops under short rotation coppice (SRC) regimes - is probably the most suited, in particular in the EU. Two issues need to be addressed before the efficacy of bio-energy for carbon mitigation can be conclusively assessed, i.e. (i) a full life cycle analysis (LCA) of the global warming contribution of SRC, and (ii) and an assessment of the energy efficiency of the system. The objectives of this project are: (i) to make a full LCA balance of the most important greenhouse gases (CO2, CH4, N2O, H2O and O3) and of the volatile organic compounds (VOC s), and (ii) to make a full energy accounting of a SRC plantation with fast-growing trees. The project will involve both an experimental approach at a representative field site in Belgium and a modelling part. For the experimental approach a SRC of poplar (Populus) will be monitored during the course of 1+3 years, harvested and transformed into bio-energy. Eddy covariance techniques will be used to monitor net fluxes of all greenhouse gases and VOC's, in combination with common assessments of biomass pools (incl. soil) and fluxes. For the energy accounting we will use life cycle analysis and energy efficiency assessments over the entire life cycle of the SRC plantation until the production of electricity and heat. A significant process based modeling component will integrate the collected knowledge on the greenhouse gas and energy balances toward predictions and simulations of the net reduction of fossil greenhouse gas emissions (avoided emissions) of SRC over different rotation cycles, global warming scenarios, and management strategies.
Max ERC Funding
2 500 000 €
Duration
Start date: 2009-03-01, End date: 2014-10-31
Project acronym POPMET
Project Large-scale identification of secondary metabolites, metabolic pathways and their genes in the model tree poplar
Researcher (PI) Wout BOERJAN
Host Institution (HI) VIB
Call Details Advanced Grant (AdG), LS9, ERC-2018-ADG
Summary Poplar is an important woody biomass crop and at the same time the model of choice for molecular research in trees. Although there is steady progress in resolving the functions of unknown genes, the identities of most secondary metabolites in poplar remain unknown. The lack of metabolite identities in experimental systems is a true gap in information content, and impedes obtaining deep insight into the complex biology of living systems. The main reason is that metabolites are difficult to purify because of their low abundance, hindering their structural characterization and the discovery of their biosynthetic pathways. In this project, we will use CSPP, an innovative method recently developed in my lab, to systematically predict the structures of metabolites along with their biosynthetic pathways in poplar wood, bark and leaves. This CSPP method is based on a combination of metabolomics and informatics. In a next step, the CSPP tool will be combined with two complementary genetic approaches based on re-sequence data from 750 poplar trees to identify the genes encoding the enzymes in the predicted pathways. Genome Wide Association Studies (GWAS) will be made to identify SNPs in the genes involved in the metabolic conversions. Subsequently, rare defective alleles will be identified for these genes in the sequenced population. Genes identified by both approaches will then be further studied either by crossing natural poplars that are heterozygous for the defective alleles, or by CRISPR/Cas9-based gene editing in poplar. The functional studies will be further underpinned by enzyme assays. Given our scarce knowledge on the structure of most secondary metabolites and their metabolic pathways in poplar, this large-scale identification effort will lay the foundation for systems biology research in this species, and will shape opportunities to further develop poplar as an industrial wood-producing crop.
Summary
Poplar is an important woody biomass crop and at the same time the model of choice for molecular research in trees. Although there is steady progress in resolving the functions of unknown genes, the identities of most secondary metabolites in poplar remain unknown. The lack of metabolite identities in experimental systems is a true gap in information content, and impedes obtaining deep insight into the complex biology of living systems. The main reason is that metabolites are difficult to purify because of their low abundance, hindering their structural characterization and the discovery of their biosynthetic pathways. In this project, we will use CSPP, an innovative method recently developed in my lab, to systematically predict the structures of metabolites along with their biosynthetic pathways in poplar wood, bark and leaves. This CSPP method is based on a combination of metabolomics and informatics. In a next step, the CSPP tool will be combined with two complementary genetic approaches based on re-sequence data from 750 poplar trees to identify the genes encoding the enzymes in the predicted pathways. Genome Wide Association Studies (GWAS) will be made to identify SNPs in the genes involved in the metabolic conversions. Subsequently, rare defective alleles will be identified for these genes in the sequenced population. Genes identified by both approaches will then be further studied either by crossing natural poplars that are heterozygous for the defective alleles, or by CRISPR/Cas9-based gene editing in poplar. The functional studies will be further underpinned by enzyme assays. Given our scarce knowledge on the structure of most secondary metabolites and their metabolic pathways in poplar, this large-scale identification effort will lay the foundation for systems biology research in this species, and will shape opportunities to further develop poplar as an industrial wood-producing crop.
Max ERC Funding
2 499 251 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
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