Project acronym APHIDTRAP
Project Understanding and Preventing Plant Susceptibility to Aphids
Researcher (PI) Jorunn Bos
Host Institution (HI) UNIVERSITY OF DUNDEE
Country United Kingdom
Call Details Consolidator Grant (CoG), LS9, ERC-2020-COG
Summary Aphids are devastating insect pests of crops globally, and pose a major threat to food security. Crucially, there is a lack of durable genetic crop resistance against aphids, and current control relies almost exclusively on insecticides, which are costly and damaging to the environment and to which aphids develop resistance. These insects deliver proteins inside host plants, called effectors, to suppress the plant immune system and enhance susceptibility. I recently discovered that these effectors exhibit their activity via interacting with host plant proteins pointing to important conceptual parallels between plant-insect and plant-microbe interactions. This raises important new questions that urgently need to be addressed to enable development of novel protection strategies against aphids that are durable and sustainable. These are:
What is the mechanistic and structural basis of aphid effector-triggered susceptibility?
How can we interfere with aphid effector-triggered susceptibility?
APHIDTRAP will address these questions using an innovative strategy: 1) I will introduce a structural biology approach to the insect effector biology field to reveal protein 3D structures of aphid effectors and their host protein targets in bound and unbound state, and determine how mutations in these proteins affect interactions and protein functions. 2) I will use both natural variants and mutants of effectors and host protein targets, combined with in planta functional assays to explore plant-aphid molecular co-evolution. 3) I will identify host protein target interactomes and investigate how mutations affect network functionality. 4) I will use information generated in 1-3 to develop and apply a synthetic biology approach to prevent aphid effector-triggered susceptibility in potato crop plants.
APHIDTRAP’s vision is to elucidate the mechanisms that underlie susceptibility to aphids and investigate how we can interfere with these to reduce crop susceptibility to insect pests.
Summary
Aphids are devastating insect pests of crops globally, and pose a major threat to food security. Crucially, there is a lack of durable genetic crop resistance against aphids, and current control relies almost exclusively on insecticides, which are costly and damaging to the environment and to which aphids develop resistance. These insects deliver proteins inside host plants, called effectors, to suppress the plant immune system and enhance susceptibility. I recently discovered that these effectors exhibit their activity via interacting with host plant proteins pointing to important conceptual parallels between plant-insect and plant-microbe interactions. This raises important new questions that urgently need to be addressed to enable development of novel protection strategies against aphids that are durable and sustainable. These are:
What is the mechanistic and structural basis of aphid effector-triggered susceptibility?
How can we interfere with aphid effector-triggered susceptibility?
APHIDTRAP will address these questions using an innovative strategy: 1) I will introduce a structural biology approach to the insect effector biology field to reveal protein 3D structures of aphid effectors and their host protein targets in bound and unbound state, and determine how mutations in these proteins affect interactions and protein functions. 2) I will use both natural variants and mutants of effectors and host protein targets, combined with in planta functional assays to explore plant-aphid molecular co-evolution. 3) I will identify host protein target interactomes and investigate how mutations affect network functionality. 4) I will use information generated in 1-3 to develop and apply a synthetic biology approach to prevent aphid effector-triggered susceptibility in potato crop plants.
APHIDTRAP’s vision is to elucidate the mechanisms that underlie susceptibility to aphids and investigate how we can interfere with these to reduce crop susceptibility to insect pests.
Max ERC Funding
1 999 992 €
Duration
Start date: 2021-06-01, End date: 2026-05-31
Project acronym BEE NATURAL
Project A sustainable future for honeybees by unravelling the mechanisms of natural disease resistance
Researcher (PI) Barbara Locke Grander
Host Institution (HI) SVERIGES LANTBRUKSUNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS9, ERC-2020-STG
Summary The ectoparasitic mite, Varroa destructor, vectors lethal honeybee viruses, in particular Deformed wing virus (DWV) and is unarguably the leading cause of honeybee (Apis mellifera) colony mortality world-wide causing critical economic and ecological consequences for pollination-dependent crop production and wild plant biodiversity, respectively. Since the introduction of the mite in the 1970s and 1980s, wild honeybees in Europe and North America have been nearly completely eradicated and managed honeybees only survive through mite control treatment, or otherwise die within 1-2 years. These treatments remove the selective pressure necessary to establish a stable host-parasite relationship, which hampers the evolution of resistance and obstructs fundamental research on natural selection host‒parasite coevolution in this new host‒parasite system, which is now only possible in a few small honeybee populations surviving long-term (>20 years) without varroa control in Sweden, France and Norway. These rare and valuable naturally selected populations offer unique insight into the natural adaptive capacity of honeybees, yet little is understood about their mechanisms of resistance or tolerance to varroa mites and the viruses they vector.
Having exclusive access to these populations, the BEE NATURAL project sets out to comprehensively describe their host resistant and tolerant phenotypes towards both mites and viruses, using a variety of innovative experimental designs, in order to deeper our fundamental understanding of host-parasite interactions. Genomic regions or target genes associated with resistant and tolerant traits will be identified using Next Generation Sequencing (NGS) technologies such as RNA-seq and whole genome sequencing (WGS), providing valuable information that can be applied towards developing marker-assisted selection: a powerful new approach for disease resistant breeding that can facilitate major advances in genetic stock improvement.
Summary
The ectoparasitic mite, Varroa destructor, vectors lethal honeybee viruses, in particular Deformed wing virus (DWV) and is unarguably the leading cause of honeybee (Apis mellifera) colony mortality world-wide causing critical economic and ecological consequences for pollination-dependent crop production and wild plant biodiversity, respectively. Since the introduction of the mite in the 1970s and 1980s, wild honeybees in Europe and North America have been nearly completely eradicated and managed honeybees only survive through mite control treatment, or otherwise die within 1-2 years. These treatments remove the selective pressure necessary to establish a stable host-parasite relationship, which hampers the evolution of resistance and obstructs fundamental research on natural selection host‒parasite coevolution in this new host‒parasite system, which is now only possible in a few small honeybee populations surviving long-term (>20 years) without varroa control in Sweden, France and Norway. These rare and valuable naturally selected populations offer unique insight into the natural adaptive capacity of honeybees, yet little is understood about their mechanisms of resistance or tolerance to varroa mites and the viruses they vector.
Having exclusive access to these populations, the BEE NATURAL project sets out to comprehensively describe their host resistant and tolerant phenotypes towards both mites and viruses, using a variety of innovative experimental designs, in order to deeper our fundamental understanding of host-parasite interactions. Genomic regions or target genes associated with resistant and tolerant traits will be identified using Next Generation Sequencing (NGS) technologies such as RNA-seq and whole genome sequencing (WGS), providing valuable information that can be applied towards developing marker-assisted selection: a powerful new approach for disease resistant breeding that can facilitate major advances in genetic stock improvement.
Max ERC Funding
1 499 703 €
Duration
Start date: 2021-03-01, End date: 2026-02-28
Project acronym CoralStem
Project Stem cell isolation and transplantation in Hexacorallia: Toward cell-therapy for corals
Researcher (PI) Benyamin ROSENTAL
Host Institution (HI) BEN-GURION UNIVERSITY OF THE NEGEV
Country Israel
Call Details Starting Grant (StG), LS9, ERC-2020-STG
Summary Reef corals are the foundation of ecosystems that host much of the ocean’s biodiversity, making them a significant component of economies and communities around the world. They are under severe threat from anthropogenic stressors, particularly global warming. Some parts of the world’s oceans have already lost the majority of their corals.
Efforts to mitigate the damage are informed by research on understanding and transferring naturally-occurring resilient genotypes. This has a direct parallel in medicine; cell- or gene-therapy, which is founded on an ability to isolate and then transplant progenitor/stem cells. This technology does not exist for any coral species.
In this research program we will develop robust tools for the isolation, characterization, and transplantation of coral progenitor cells. The tools will be species non-specific, and therefore widely applicable.
We will develop generalized strategies for isolating cell-type enriched cell populations, especially progenitor cells, in four species of anemones and stony corals. We will develop cell transplantation techniques for engraftment in non-model species. We will then characterize the engraftment potentials of candidate progenitor cell populations in these species.
This technology will have an impact on basic and applied research. Because of the broad applicability, it will become a valuable tool for researchers seeking a more complete cell biology in non-classical invertebrate species. Being able to isolate, manipulate, and replace progenitor cells in diverse species will assist in efforts to understand how the developmental programs that construct or regenerate an organism function and change during evolution. Being able to transfer progenitor cells from a stress-resilient coral to a sensitive one will assist in understanding the mechanisms governing stress tolerance. With this research, and using the tools developed here, it may become possible to confer resilience in the wild.
Summary
Reef corals are the foundation of ecosystems that host much of the ocean’s biodiversity, making them a significant component of economies and communities around the world. They are under severe threat from anthropogenic stressors, particularly global warming. Some parts of the world’s oceans have already lost the majority of their corals.
Efforts to mitigate the damage are informed by research on understanding and transferring naturally-occurring resilient genotypes. This has a direct parallel in medicine; cell- or gene-therapy, which is founded on an ability to isolate and then transplant progenitor/stem cells. This technology does not exist for any coral species.
In this research program we will develop robust tools for the isolation, characterization, and transplantation of coral progenitor cells. The tools will be species non-specific, and therefore widely applicable.
We will develop generalized strategies for isolating cell-type enriched cell populations, especially progenitor cells, in four species of anemones and stony corals. We will develop cell transplantation techniques for engraftment in non-model species. We will then characterize the engraftment potentials of candidate progenitor cell populations in these species.
This technology will have an impact on basic and applied research. Because of the broad applicability, it will become a valuable tool for researchers seeking a more complete cell biology in non-classical invertebrate species. Being able to isolate, manipulate, and replace progenitor cells in diverse species will assist in efforts to understand how the developmental programs that construct or regenerate an organism function and change during evolution. Being able to transfer progenitor cells from a stress-resilient coral to a sensitive one will assist in understanding the mechanisms governing stress tolerance. With this research, and using the tools developed here, it may become possible to confer resilience in the wild.
Max ERC Funding
2 045 900 €
Duration
Start date: 2021-03-01, End date: 2026-02-28
Project acronym CPTarget
Project Cyclic Peptide Platform as an Approach to Target Validation
Researcher (PI) Akane Kawamura
Host Institution (HI) UNIVERSITY OF NEWCASTLE UPON TYNE
Country United Kingdom
Call Details Consolidator Grant (CoG), LS9, ERC-2020-COG
Summary The current ‘genomics’ era is an exciting time for drug target discovery with considerable opportunities for therapeutic intervention. Whilst classical small molecules remain the reagents of choice as chemical probes for target validation, not all targets are tractable with small molecules. There is thus an urgent need to develop methods for more efficient target validation, not only of individual proteins but also of protein-protein and other complexes.
Natural product like cyclic peptides have enormous potential as a chemical platform for target validation. Recent technological advances have enabled the efficient production and screening of large libraries containing non-proteinogenic residues. De novo cyclic peptides with high affinity and selectivity for target proteins can be readily generated, even for protein-protein interaction targets perceived as challenging. Development of this technology and their innovative applications as outlined in our proposal will provide a step-change in methodology, and transform the current approach for studying the biological function of the target / pathways, enabling new ways to investigate potential targets.
We aim to develop innovative chemical and molecular techniques to explore the applications of natural product-like cyclic peptides in target validation for very challenging targets. Ultimately the work aims to enable the development of new therapeutic agents targeting multiple diseases.
Summary
The current ‘genomics’ era is an exciting time for drug target discovery with considerable opportunities for therapeutic intervention. Whilst classical small molecules remain the reagents of choice as chemical probes for target validation, not all targets are tractable with small molecules. There is thus an urgent need to develop methods for more efficient target validation, not only of individual proteins but also of protein-protein and other complexes.
Natural product like cyclic peptides have enormous potential as a chemical platform for target validation. Recent technological advances have enabled the efficient production and screening of large libraries containing non-proteinogenic residues. De novo cyclic peptides with high affinity and selectivity for target proteins can be readily generated, even for protein-protein interaction targets perceived as challenging. Development of this technology and their innovative applications as outlined in our proposal will provide a step-change in methodology, and transform the current approach for studying the biological function of the target / pathways, enabling new ways to investigate potential targets.
We aim to develop innovative chemical and molecular techniques to explore the applications of natural product-like cyclic peptides in target validation for very challenging targets. Ultimately the work aims to enable the development of new therapeutic agents targeting multiple diseases.
Max ERC Funding
2 241 271 €
Duration
Start date: 2021-10-01, End date: 2026-09-30
Project acronym DEUSBIO
Project Deciphering and Engineering the overlooked but Universal phenomenon of Subpopulations in BIOtechnology
Researcher (PI) Rodrigo Ledesma Amaro
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Country United Kingdom
Call Details Starting Grant (StG), LS9, ERC-2020-STG
Summary Microbial bioproduction, despite being considered a paradigmatic sustainable alternative to petroleum-based chemistry, is often limited by low yields and productivities, which prevents commercialisation. It is generally known for all types of cells that genetically identical populations can form metabolically distinct subpopulations. This diversity strongly impairs bioproduction as the presence of low-producer or slow-grower cells reduces overall yields. However, the universal phenomenon of subpopulations emergence has been largely overlooked, especially in biotechnology, due to technical difficulties. Now, thanks to recent developments in single cell technologies, in molecular understanding of microbial communities and in synthetic biology tools, we can begin to address this widespread and impactful biological feature.
I propose to explore the emergence of subpopulations in yeast and understand their implications in metabolism and bioproduction using and developing cutting edge synthetic biology tools. I aim to use that knowledge to develop novel engineered strains that lack the presence of undesired subpopulations and then use such homogeneous populations for bioproduction. The homogenised production will be investigated in both, monocultures and microbial communities. In DEUSBIO, I will set up an innovative framework to maximise the biosynthesis of high value molecules, with high potential to overcome current limitations.
This project will shed light on the phenomenon of subpopulations, whose relevance goes beyond bioproduction, as for example, it has been associated with the origin of multicellularity. Increasing our knowledge about this matter will also have implications in biomedicine, as cell subpopulations are extremely important in the appearance of antimicrobial resistant, in cancer heterogeneity, and in microbiome complexity.
Summary
Microbial bioproduction, despite being considered a paradigmatic sustainable alternative to petroleum-based chemistry, is often limited by low yields and productivities, which prevents commercialisation. It is generally known for all types of cells that genetically identical populations can form metabolically distinct subpopulations. This diversity strongly impairs bioproduction as the presence of low-producer or slow-grower cells reduces overall yields. However, the universal phenomenon of subpopulations emergence has been largely overlooked, especially in biotechnology, due to technical difficulties. Now, thanks to recent developments in single cell technologies, in molecular understanding of microbial communities and in synthetic biology tools, we can begin to address this widespread and impactful biological feature.
I propose to explore the emergence of subpopulations in yeast and understand their implications in metabolism and bioproduction using and developing cutting edge synthetic biology tools. I aim to use that knowledge to develop novel engineered strains that lack the presence of undesired subpopulations and then use such homogeneous populations for bioproduction. The homogenised production will be investigated in both, monocultures and microbial communities. In DEUSBIO, I will set up an innovative framework to maximise the biosynthesis of high value molecules, with high potential to overcome current limitations.
This project will shed light on the phenomenon of subpopulations, whose relevance goes beyond bioproduction, as for example, it has been associated with the origin of multicellularity. Increasing our knowledge about this matter will also have implications in biomedicine, as cell subpopulations are extremely important in the appearance of antimicrobial resistant, in cancer heterogeneity, and in microbiome complexity.
Max ERC Funding
1 499 998 €
Duration
Start date: 2021-03-01, End date: 2026-02-28
Project acronym DIVERSIPHAGY
Project Utilizing diversity to decipher the role of autophagy in plant-microbe interactions
Researcher (PI) Suayb uestuen
Host Institution (HI) EBERHARD KARLS UNIVERSITAET TUEBINGEN
Country Germany
Call Details Starting Grant (StG), LS9, ERC-2020-STG
Summary During the course of evolution, plants have been exposed to a plethora of beneficial and pathogenic microbes. While symbionts are beneficial for the host plant by improving nutrient supply and health, pathogens are reprogramming their host only for their own benefit. At the interface of this interaction proteomes at both sides are highly flexible and require regulated protein turnover. In line with this, our previous work revealed that regulated protein degradation by autophagy is an essential player in plant immunity. Consequently, plant pathogens hijack autophagy during binary interactions though in contrasting manners. However, in a more complete scenario, plants are constantly exposed to different microbes and hence it is crucial to include the microbial diversity into this equation to obtain a holistic picture of the role of autophagy in plant-microbe interactions. The picture is getting even more complex if we look at the cellular diversity on the host side. Thus, DIVERSIPHAGY approaches the role of autophagy through bacterial and cellular diversity on the host side. We aim to address following questions:
• Identifying how the bacterial diversity impacts autophagy and vice versa
• Determining new bacteria and/or bacterial communities hijacking autophagy
• Revealing the autophagy degradome and novel autophagy factors by utilizing autophagy-modulating bacteria
• Identifying tissue and cell-type specific modulation of autophagy by diverse bacteria.
With DIVERSIPHAGY we will reveal the holistic picture of the role of autophagy in plant-microbe interactions using a mixture of state-of-the-art approaches including metabolomics, proteomics, single-cell transcriptomics and cell-type specific reverse genetic screens. As such DIVERSIPHAGY is the next generation approach to understand the role of plant autophagy in plant-microbe interactions and by translating our results into crop plants we will be able to develop more durable resistances toward destructive pathogens.
Summary
During the course of evolution, plants have been exposed to a plethora of beneficial and pathogenic microbes. While symbionts are beneficial for the host plant by improving nutrient supply and health, pathogens are reprogramming their host only for their own benefit. At the interface of this interaction proteomes at both sides are highly flexible and require regulated protein turnover. In line with this, our previous work revealed that regulated protein degradation by autophagy is an essential player in plant immunity. Consequently, plant pathogens hijack autophagy during binary interactions though in contrasting manners. However, in a more complete scenario, plants are constantly exposed to different microbes and hence it is crucial to include the microbial diversity into this equation to obtain a holistic picture of the role of autophagy in plant-microbe interactions. The picture is getting even more complex if we look at the cellular diversity on the host side. Thus, DIVERSIPHAGY approaches the role of autophagy through bacterial and cellular diversity on the host side. We aim to address following questions:
• Identifying how the bacterial diversity impacts autophagy and vice versa
• Determining new bacteria and/or bacterial communities hijacking autophagy
• Revealing the autophagy degradome and novel autophagy factors by utilizing autophagy-modulating bacteria
• Identifying tissue and cell-type specific modulation of autophagy by diverse bacteria.
With DIVERSIPHAGY we will reveal the holistic picture of the role of autophagy in plant-microbe interactions using a mixture of state-of-the-art approaches including metabolomics, proteomics, single-cell transcriptomics and cell-type specific reverse genetic screens. As such DIVERSIPHAGY is the next generation approach to understand the role of plant autophagy in plant-microbe interactions and by translating our results into crop plants we will be able to develop more durable resistances toward destructive pathogens.
Max ERC Funding
1 499 462 €
Duration
Start date: 2021-03-01, End date: 2026-02-28
Project acronym EXPLORE
Project Exploitation of enzyme promiscuity to generate ribosomal natural product diversity
Researcher (PI) Jesko KOEHNKE
Host Institution (HI) UNIVERSITY OF GLASGOW
Country United Kingdom
Call Details Consolidator Grant (CoG), LS9, ERC-2020-COG
Summary Natural sources have been highly important for the discovery of new drugs, offering compounds that possess exciting and potent bioactivities. The development of many promising natural products is significantly hampered by the difficulties associated with the synthesis of novel analogs. The family of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products offers a plethora of different, promising bioactivities and highly diverse scaffolds. I propose to develop two new complementary routes to generate modified, bespoke RiPPs in vitro and in vivo: Interchangeable leader peptide (ILP) technology, which is a novel approach tailored to RiPPs. Every RiPP is produced from a precursor peptide that consists of a core peptide (the eventual natural product) and a pathway-specific recognition sequence that is recognized by parts of the biosynthetic machinery. ILP technology will allow me to swap out recognition sequences and thus combine the biosynthetic machineries from diverse RiPP pathways in a mix-and-match approach to generate new-to-nature, hybrid RiPPs using two routes: (1) We will develop this technology in vitro to take full advantage of non-natural amino acids and other building blocks. (2) We will transfer an optimized, streamlined version to an in vivo setting using peptide ligation in the cytoplasm of E. coli. This will allow us to use the power of genetics to create large libraries of compounds. I will harvest the novel enzymatic modifications enabled by ILPs to generate diverse RiPP scaffolds that contain amino acids, non-natural amino acids, enzymatically modified amino acids and non-a-amino acid building blocks. We will then use ILP technology to identify novel pathoblockers for Pseudomonas aeruginosa. The successful completion of this project will revolutionize the design of RiPPs-inspired next generation libraries with diverse scaffolds for application in tool compound development, target identification and drug discovery.
Summary
Natural sources have been highly important for the discovery of new drugs, offering compounds that possess exciting and potent bioactivities. The development of many promising natural products is significantly hampered by the difficulties associated with the synthesis of novel analogs. The family of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products offers a plethora of different, promising bioactivities and highly diverse scaffolds. I propose to develop two new complementary routes to generate modified, bespoke RiPPs in vitro and in vivo: Interchangeable leader peptide (ILP) technology, which is a novel approach tailored to RiPPs. Every RiPP is produced from a precursor peptide that consists of a core peptide (the eventual natural product) and a pathway-specific recognition sequence that is recognized by parts of the biosynthetic machinery. ILP technology will allow me to swap out recognition sequences and thus combine the biosynthetic machineries from diverse RiPP pathways in a mix-and-match approach to generate new-to-nature, hybrid RiPPs using two routes: (1) We will develop this technology in vitro to take full advantage of non-natural amino acids and other building blocks. (2) We will transfer an optimized, streamlined version to an in vivo setting using peptide ligation in the cytoplasm of E. coli. This will allow us to use the power of genetics to create large libraries of compounds. I will harvest the novel enzymatic modifications enabled by ILPs to generate diverse RiPP scaffolds that contain amino acids, non-natural amino acids, enzymatically modified amino acids and non-a-amino acid building blocks. We will then use ILP technology to identify novel pathoblockers for Pseudomonas aeruginosa. The successful completion of this project will revolutionize the design of RiPPs-inspired next generation libraries with diverse scaffolds for application in tool compound development, target identification and drug discovery.
Max ERC Funding
1 977 125 €
Duration
Start date: 2021-06-01, End date: 2026-05-31
Project acronym FORWARD
Project Causes and consequences of forest reorganization: Towards understanding forest change
Researcher (PI) Rupert Seidl
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Country Germany
Call Details Consolidator Grant (CoG), LS9, ERC-2020-COG
Summary Forest ecosystems around the globe are undergoing rapid reorganization. The unabated continuation of climate change, the accelerating rate of alien species introductions, and the precipitous loss of biological diversity are altering the structure and composition of forest ecosystems. As a consequence, novel ecosystems are emerging. However, the trajectories to novelty and the consequences thereof remain widely unknown. This limits the ability of forest policy and management to counteract undesired developments and safeguard the supply of ecosystem services to society. Here I will investigate the causes and consequences of reorganization in forest ecosystems. I will use a concerted combination of complementary methodological approaches to understand why reorganization takes place, when and where reorganization is likely to happen, and what impacts reorganization will have on biodiversity and ecosystem services. Replicated experiments will be conducted both in the field and in walk-in climate chambers to answer whether compounding climatic extremes could result in bottlenecks of forest regeneration. A next-generation forest landscape model will be developed to investigate how invasive alien species alter forest development. Based on these insights the FORWARD project will derive operational early warning indicators of reorganization, and test their generality and applicability in the field for landscapes on three continents. Subsequently, a machine-learning aided synthesis of big datasets will be used to compile the first map of global hotspots of forest reorganization. Finally, robust management strategies for addressing reorganization will be developed. Jointly studying the effects of global change on tree mortality and regeneration across scales, the FORWARD project will bring about a new level of understanding of forest change, and will provide the data, tools and strategies to tackle one of the most pressing challenges of current forest policy and management.
Summary
Forest ecosystems around the globe are undergoing rapid reorganization. The unabated continuation of climate change, the accelerating rate of alien species introductions, and the precipitous loss of biological diversity are altering the structure and composition of forest ecosystems. As a consequence, novel ecosystems are emerging. However, the trajectories to novelty and the consequences thereof remain widely unknown. This limits the ability of forest policy and management to counteract undesired developments and safeguard the supply of ecosystem services to society. Here I will investigate the causes and consequences of reorganization in forest ecosystems. I will use a concerted combination of complementary methodological approaches to understand why reorganization takes place, when and where reorganization is likely to happen, and what impacts reorganization will have on biodiversity and ecosystem services. Replicated experiments will be conducted both in the field and in walk-in climate chambers to answer whether compounding climatic extremes could result in bottlenecks of forest regeneration. A next-generation forest landscape model will be developed to investigate how invasive alien species alter forest development. Based on these insights the FORWARD project will derive operational early warning indicators of reorganization, and test their generality and applicability in the field for landscapes on three continents. Subsequently, a machine-learning aided synthesis of big datasets will be used to compile the first map of global hotspots of forest reorganization. Finally, robust management strategies for addressing reorganization will be developed. Jointly studying the effects of global change on tree mortality and regeneration across scales, the FORWARD project will bring about a new level of understanding of forest change, and will provide the data, tools and strategies to tackle one of the most pressing challenges of current forest policy and management.
Max ERC Funding
1 965 293 €
Duration
Start date: 2021-10-01, End date: 2026-09-30
Project acronym hOssicle
Project Bioengineering of human ossicles as advanced in vivo hematopoietic model
Researcher (PI) Paul Bourgine
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS9, ERC-2020-STG
Summary hOssicle aims at developing miniaturized human bone organs in mice to be used as advanced model of healthy and malignant human hematopoiesis.
In Europe, 80 million people are estimated to suffer from blood disorders. When at all existing, treatments are poorly effective: 92 % of new drugs successful in preclinical testing (animals and in vitro culture systems) fail in clinical trials. This urgently calls for the development of superior models, to refine our understanding of human hematopoiesis and better predict patient´ therapy efficacy.
My laboratory has developed unique human mesenchymal lines capable of forming “human ossicles” by recapitulation of endochondral ossification -the developmental process of bone formation. These ossicles form subcutaneously in mice and display a similar structure and function to native mouse bones, but rely on human mesenchymal cells reconstituting a complex bone marrow environment specifically supporting the development of human hematopoiesis.
hOssicle will offer the unprecedented custom engineering of human bones to understand the functional organization of its hematopoietic compartment. By genetic reprogramming of mesenchymal lines, I aim at controlling the molecular and cellular composition of the ossicles and study the corresponding impact on hematopoietic development. Finally, I envision the engineering of patient-specific ossicles with mesenchymal and leukemic blood cells from the same individual towards recapitulation of the disease setting. This will be a significant breakthrough, by offering the study of malignancy progression and drug-testing in a personalized in vivo context for cancer remission.
By combining principles of bone development & tissue engineering, hOssicle proposes an “organ engineering” approach applied to hematopoiesis. The implications run from the identification of key factors controlling the production of blood cell types to the personalized modelling of leukemia and test of therapies.
Summary
hOssicle aims at developing miniaturized human bone organs in mice to be used as advanced model of healthy and malignant human hematopoiesis.
In Europe, 80 million people are estimated to suffer from blood disorders. When at all existing, treatments are poorly effective: 92 % of new drugs successful in preclinical testing (animals and in vitro culture systems) fail in clinical trials. This urgently calls for the development of superior models, to refine our understanding of human hematopoiesis and better predict patient´ therapy efficacy.
My laboratory has developed unique human mesenchymal lines capable of forming “human ossicles” by recapitulation of endochondral ossification -the developmental process of bone formation. These ossicles form subcutaneously in mice and display a similar structure and function to native mouse bones, but rely on human mesenchymal cells reconstituting a complex bone marrow environment specifically supporting the development of human hematopoiesis.
hOssicle will offer the unprecedented custom engineering of human bones to understand the functional organization of its hematopoietic compartment. By genetic reprogramming of mesenchymal lines, I aim at controlling the molecular and cellular composition of the ossicles and study the corresponding impact on hematopoietic development. Finally, I envision the engineering of patient-specific ossicles with mesenchymal and leukemic blood cells from the same individual towards recapitulation of the disease setting. This will be a significant breakthrough, by offering the study of malignancy progression and drug-testing in a personalized in vivo context for cancer remission.
By combining principles of bone development & tissue engineering, hOssicle proposes an “organ engineering” approach applied to hematopoiesis. The implications run from the identification of key factors controlling the production of blood cell types to the personalized modelling of leukemia and test of therapies.
Max ERC Funding
1 500 000 €
Duration
Start date: 2021-05-01, End date: 2026-04-30
Project acronym HUMYCO
Project Investigating the Human Mycobolome through Uniting Large-scale Epidemiological and Mechanistic Poly-omic Designs
Researcher (PI) Marthe DE BOEVRE
Host Institution (HI) UNIVERSITEIT GENT
Country Belgium
Call Details Starting Grant (StG), LS9, ERC-2020-STG
Summary Mycotoxins, toxic fungal secondary metabolites, known to be the most hazardous of all food contaminants in terms of chronic toxicity, have the potential to contribute to a diversity of adverse health effects in humans, and are unfortunately ubiquitously present in our daily diet. Chronic low-dose intake of multiple mycotoxins are hypothesized to be associated with an increased risk of developing human renal, colorectal and hepatocellular carcinomas. HUMYCO refers to a unique, holistic & multi(cross)-disciplinary research field, aiming at comprehensively investigating the human mycobolome through uniting large-scale epidemiological & mechanistic designs using a poly-omic approach. Focus is set to generate newly hypotheses-driven insights into the role of multiple mycotoxin exposure in the aetiology of human carcinomas. The capability of conducting accurate exposure assessments of mycotoxins at the individual-level is required to fully understand the potential health consequences in humans, therefore, mycotoxin biomarkers of exposure will be primarily identified in vitro, and validated using human intervention studies by elucidating human mycotoxicokinetic profiles via metabolomics. The nature and extent of associations between estimated external and internal dietary multiple mycotoxin exposures and developing renal, colorectal and hepatocellular carcinomas will be investigated through large-scale epidemiological bio-cohorts, established in both Europe and Africa. To further disentangle possible associative mycotoxin-induced cancer development, causal relations will be verified through an innovative mechanistic arm applying advanced cutting-edged technologies. For the first time, genome-wide mutation spectra associated with multi-exposure to putatively carcinogenic mycotoxins will be experimentally determined. HUMYCO contributes to dietary-based human health prevention by identification of specific cancer risks related to multiple mycotoxins exposure.
Summary
Mycotoxins, toxic fungal secondary metabolites, known to be the most hazardous of all food contaminants in terms of chronic toxicity, have the potential to contribute to a diversity of adverse health effects in humans, and are unfortunately ubiquitously present in our daily diet. Chronic low-dose intake of multiple mycotoxins are hypothesized to be associated with an increased risk of developing human renal, colorectal and hepatocellular carcinomas. HUMYCO refers to a unique, holistic & multi(cross)-disciplinary research field, aiming at comprehensively investigating the human mycobolome through uniting large-scale epidemiological & mechanistic designs using a poly-omic approach. Focus is set to generate newly hypotheses-driven insights into the role of multiple mycotoxin exposure in the aetiology of human carcinomas. The capability of conducting accurate exposure assessments of mycotoxins at the individual-level is required to fully understand the potential health consequences in humans, therefore, mycotoxin biomarkers of exposure will be primarily identified in vitro, and validated using human intervention studies by elucidating human mycotoxicokinetic profiles via metabolomics. The nature and extent of associations between estimated external and internal dietary multiple mycotoxin exposures and developing renal, colorectal and hepatocellular carcinomas will be investigated through large-scale epidemiological bio-cohorts, established in both Europe and Africa. To further disentangle possible associative mycotoxin-induced cancer development, causal relations will be verified through an innovative mechanistic arm applying advanced cutting-edged technologies. For the first time, genome-wide mutation spectra associated with multi-exposure to putatively carcinogenic mycotoxins will be experimentally determined. HUMYCO contributes to dietary-based human health prevention by identification of specific cancer risks related to multiple mycotoxins exposure.
Max ERC Funding
1 498 750 €
Duration
Start date: 2020-12-01, End date: 2025-11-30
