Project acronym ELONGAN
Project Gene editing and in vitro approaches to understand conceptus elongation in ungulates
Researcher (PI) Pablo BERMEJO-ÁLVAREZ
Host Institution (HI) INSTITUTO NACIONAL DE INVESTIGACION Y TECNOLOGIA AGRARIA Y ALIMENTARIA OA MP
Call Details Starting Grant (StG), LS9, ERC-2017-STG
Summary In contrast to human or rodent embryos, ungulate embryos do not implant into the uterus right after blastocyst hatching. Before implantation, the hatched ungulate blastocyst must undergo dramatic morphological changes characterized by cell differentiation, proliferation and migration processes leading to the development of extra-embryonic membranes, the appearance of a flat embryonic disc and gastrulation. This prolonged preimplantation development is termed conceptus elongation and deficiencies on this process constitute the most frequent cause of reproductive failures in ungulates, including the 4 most relevant mammalian livestock species in Europe. The purpose of this project is to elucidate the factors involved in conceptus elongation by gene editing and in vitro culture approaches. A first objective will be to identify key genes involved in differentiation processes by RNA-seq analysis of different embryo derivatives from bovine conceptuses at different developmental stages. Subsequently, the function of some of the genes identified as well as others known to play a crucial role in mouse development or putatively involved in embryo-maternal interactions will be assessed. For this aim, bovine embryos in which a candidate gene has been ablated (KO) will be generated by CRISPR and transferred to recipient females to assess in vivo the function of such particular gene on conceptus development. A second set of experiments pursue the development of an in vitro system for conceptus elongation that would bypass the requirement for in vivo experiments. For this aim we will perform metabolomics and proteomics analyses of bovine uterine fluid at different stages and will use these data to rationally develop a culture system able to sustain conceptus development. The knowledge generated by this project will serve to develop strategies to enhance farming profitability by reducing embryonic loss and to understand Developmental Biology questions unanswered by the mouse model.
Summary
In contrast to human or rodent embryos, ungulate embryos do not implant into the uterus right after blastocyst hatching. Before implantation, the hatched ungulate blastocyst must undergo dramatic morphological changes characterized by cell differentiation, proliferation and migration processes leading to the development of extra-embryonic membranes, the appearance of a flat embryonic disc and gastrulation. This prolonged preimplantation development is termed conceptus elongation and deficiencies on this process constitute the most frequent cause of reproductive failures in ungulates, including the 4 most relevant mammalian livestock species in Europe. The purpose of this project is to elucidate the factors involved in conceptus elongation by gene editing and in vitro culture approaches. A first objective will be to identify key genes involved in differentiation processes by RNA-seq analysis of different embryo derivatives from bovine conceptuses at different developmental stages. Subsequently, the function of some of the genes identified as well as others known to play a crucial role in mouse development or putatively involved in embryo-maternal interactions will be assessed. For this aim, bovine embryos in which a candidate gene has been ablated (KO) will be generated by CRISPR and transferred to recipient females to assess in vivo the function of such particular gene on conceptus development. A second set of experiments pursue the development of an in vitro system for conceptus elongation that would bypass the requirement for in vivo experiments. For this aim we will perform metabolomics and proteomics analyses of bovine uterine fluid at different stages and will use these data to rationally develop a culture system able to sustain conceptus development. The knowledge generated by this project will serve to develop strategies to enhance farming profitability by reducing embryonic loss and to understand Developmental Biology questions unanswered by the mouse model.
Max ERC Funding
1 480 880 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym FORMICA
Project Microclimatic buffering of plant responses to macroclimate warming in temperate forests
Researcher (PI) Pieter DE FRENNE
Host Institution (HI) UNIVERSITEIT GENT
Call Details Starting Grant (StG), LS9, ERC-2017-STG
Summary Recent global warming is acting across ecosystems and threatening biodiversity. Yet, due to slow responses, many biological communities are lagging behind warming of the macroclimate (the climate of a large geographic region). The buffering of microclimates near the ground measured in localized areas, arising from terrain features such as vegetation and topography, can explain why many species are lagging behind macroclimate warming. However, almost all studies ignore the effects of microclimatic buffering and key uncertainties still exist about this mechanism. Microclimates are particularly evident in forests, where understorey habitats are buffered by overstorey trees. In temperate forests, the understorey contains the vast majority of plant diversity and plays an essential role in driving ecosystem processes.
The overall goal of FORMICA (FORest MICroclimate Assessment) is to quantify and understand the role of microclimatic buffering in modulating forest understorey plant responses to macroclimate warming. We will perform the best assessment to date of the effects of microclimates on plants by applying microtemperature loggers, experimental heating, fluorescent tubes and a large-scale transplant experiment in temperate forests across Europe. For the first time, plant data from the individual to ecosystem level will be related to microclimate along wide temperature gradients and forest management regimes. The empirical results will then be integrated in cutting-edge demographic distribution models to forecast plant diversity in temperate forests as macroclimate warms.
FORMICA will provide the first integrative study on microclimatic buffering of macroclimate warming in forests. Interdisciplinary concepts and methods will be applied, including from climatology, forestry and ecology. FORMICA will reshape our current understanding of the impacts of climate change on forests and help land managers and policy makers to develop urgently needed adaptation strategies.
Summary
Recent global warming is acting across ecosystems and threatening biodiversity. Yet, due to slow responses, many biological communities are lagging behind warming of the macroclimate (the climate of a large geographic region). The buffering of microclimates near the ground measured in localized areas, arising from terrain features such as vegetation and topography, can explain why many species are lagging behind macroclimate warming. However, almost all studies ignore the effects of microclimatic buffering and key uncertainties still exist about this mechanism. Microclimates are particularly evident in forests, where understorey habitats are buffered by overstorey trees. In temperate forests, the understorey contains the vast majority of plant diversity and plays an essential role in driving ecosystem processes.
The overall goal of FORMICA (FORest MICroclimate Assessment) is to quantify and understand the role of microclimatic buffering in modulating forest understorey plant responses to macroclimate warming. We will perform the best assessment to date of the effects of microclimates on plants by applying microtemperature loggers, experimental heating, fluorescent tubes and a large-scale transplant experiment in temperate forests across Europe. For the first time, plant data from the individual to ecosystem level will be related to microclimate along wide temperature gradients and forest management regimes. The empirical results will then be integrated in cutting-edge demographic distribution models to forecast plant diversity in temperate forests as macroclimate warms.
FORMICA will provide the first integrative study on microclimatic buffering of macroclimate warming in forests. Interdisciplinary concepts and methods will be applied, including from climatology, forestry and ecology. FORMICA will reshape our current understanding of the impacts of climate change on forests and help land managers and policy makers to develop urgently needed adaptation strategies.
Max ERC Funding
1 498 469 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
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 SENTIFLEX
Project Fluorescence-based photosynthesis estimates for vegetation productivity monitoring from space
Researcher (PI) Jochem VERRELST
Host Institution (HI) UNIVERSITAT DE VALENCIA
Call Details Starting Grant (StG), LS9, ERC-2017-STG
Summary Global food security will remain a worldwide concern for the next 50 years and beyond. Agricultural production undergoes an increasing pressure by global anthropogenic changes, including rising population, increased protein demands and climatic extremes. Because of the immediate and dynamic nature of these changes, productivity monitoring measures are urgently needed to ensure both the stability and continued increase of the global food supply. Europe has expressed ambitions to keep its fingers on the pulse of its agricultural lands. In response to that, this proposal - named SENTIFLEX - is dedicated to developing a European vegetation productivity monitoring facility based on the synergy of Sentinel-3 (S3) with FLEX satellite fluorescence data. ESA's 8th Earth Explorer FLEX is the first mission specifically designed to globally measure Sun-Induced chlorophyll Fluorescence (SIF) emission from terrestrial vegetation. These two European Earth observation missions offer immense possibilities to increase our knowledge of the basic functioning of the Earth’s vegetation, i.e., the photosynthetic activity of plants resulting in carbon fixation. Two complementary approaches are envisioned to realize quantification of photosynthesis through satellite SIF and S3. First, the work seeks to advance the science in establishing and consolidating relationships between canopy-leaving SIF and unbiased estimates of photosynthesis of the plants, thereby disentangling the role of dynamic vegetative and atmospheric variables. Second, consolidated relationships between SIF and photosynthesis will be used to build a FLEX-S3 data processing assimilation scheme through process-based vegetation models that will deliver spatiotemporally highly resolved information on Europe’s vegetation productivity. To streamline all these datasets into a prototype vegetation productivity monitoring facility, new data processing concepts will be introduced such as the emulation of radiative transfer models.
Summary
Global food security will remain a worldwide concern for the next 50 years and beyond. Agricultural production undergoes an increasing pressure by global anthropogenic changes, including rising population, increased protein demands and climatic extremes. Because of the immediate and dynamic nature of these changes, productivity monitoring measures are urgently needed to ensure both the stability and continued increase of the global food supply. Europe has expressed ambitions to keep its fingers on the pulse of its agricultural lands. In response to that, this proposal - named SENTIFLEX - is dedicated to developing a European vegetation productivity monitoring facility based on the synergy of Sentinel-3 (S3) with FLEX satellite fluorescence data. ESA's 8th Earth Explorer FLEX is the first mission specifically designed to globally measure Sun-Induced chlorophyll Fluorescence (SIF) emission from terrestrial vegetation. These two European Earth observation missions offer immense possibilities to increase our knowledge of the basic functioning of the Earth’s vegetation, i.e., the photosynthetic activity of plants resulting in carbon fixation. Two complementary approaches are envisioned to realize quantification of photosynthesis through satellite SIF and S3. First, the work seeks to advance the science in establishing and consolidating relationships between canopy-leaving SIF and unbiased estimates of photosynthesis of the plants, thereby disentangling the role of dynamic vegetative and atmospheric variables. Second, consolidated relationships between SIF and photosynthesis will be used to build a FLEX-S3 data processing assimilation scheme through process-based vegetation models that will deliver spatiotemporally highly resolved information on Europe’s vegetation productivity. To streamline all these datasets into a prototype vegetation productivity monitoring facility, new data processing concepts will be introduced such as the emulation of radiative transfer models.
Max ERC Funding
1 499 587 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym STRP-DIFFERENTIATION
Project BIOMOLECULAR CHARACTERIZATION OF STREPTOMYCES DIFFERENTIATION AND ITS RELATIONSHIP WITH SECONDARY METABOLITE PRODUCTION
Researcher (PI) Ángel Manteca Fernández
Host Institution (HI) UNIVERSIDAD DE OVIEDO
Call Details Starting Grant (StG), LS9, ERC-2011-StG_20101109
Summary Streptomyces is a gram positive bacterium characterized by a complex developmental cycle. It is considered as a multicellular prokaryotic model that includes programmed cell death and sporulation. Streptomycetes are very important in industry, since they produce two thirds of clinically relevant secondary metabolites. Streptomyces and other bacteria with complex life cycles represent the evolutionary origin of some of the protein domains involved in the most important eukaryotic signalling pathways.
The classical Streptomyces developmental cycle focused in the sporulation. Industrial fermentations are mainly produced in liquid cultures (large bioreactors), conditions in which there is not sporulation, and it was traditionally considered that there was no differentiation. During his predoctoral training, A. Manteca re-evaluated Streptomyces development in solid sporulating cultures, laying the foundation of a new research line about Streptomyces differentiation totally independent to the investigations of his PhD supervisor (Streptomyces nucleases). During his postdoctoral training, he continued working in this emerging research line analyzing the relation between differentiation and secondary metabolite production, reporting the first study in which antibiotic production could be associated with hyphae differentiation in liquid. Later, he focused in the proteomic analysis of Streptomyces differentiation, creating the most complete database about proteome variations associated with hyphae differentiation.
The main objective of this project will be characterizing the biomolecular pathways behind Streptomyces differentiation, and their homologies and differences with eukaryotic signalling pathways. We will use the innovative developmental model elaborated by us and the information about the proteome differences during Streptomyces differentiation, to perform large scale mutagenesis and exhaustive phenotypic / bioinformatic characterization of these mutants.
Summary
Streptomyces is a gram positive bacterium characterized by a complex developmental cycle. It is considered as a multicellular prokaryotic model that includes programmed cell death and sporulation. Streptomycetes are very important in industry, since they produce two thirds of clinically relevant secondary metabolites. Streptomyces and other bacteria with complex life cycles represent the evolutionary origin of some of the protein domains involved in the most important eukaryotic signalling pathways.
The classical Streptomyces developmental cycle focused in the sporulation. Industrial fermentations are mainly produced in liquid cultures (large bioreactors), conditions in which there is not sporulation, and it was traditionally considered that there was no differentiation. During his predoctoral training, A. Manteca re-evaluated Streptomyces development in solid sporulating cultures, laying the foundation of a new research line about Streptomyces differentiation totally independent to the investigations of his PhD supervisor (Streptomyces nucleases). During his postdoctoral training, he continued working in this emerging research line analyzing the relation between differentiation and secondary metabolite production, reporting the first study in which antibiotic production could be associated with hyphae differentiation in liquid. Later, he focused in the proteomic analysis of Streptomyces differentiation, creating the most complete database about proteome variations associated with hyphae differentiation.
The main objective of this project will be characterizing the biomolecular pathways behind Streptomyces differentiation, and their homologies and differences with eukaryotic signalling pathways. We will use the innovative developmental model elaborated by us and the information about the proteome differences during Streptomyces differentiation, to perform large scale mutagenesis and exhaustive phenotypic / bioinformatic characterization of these mutants.
Max ERC Funding
1 341 985 €
Duration
Start date: 2012-01-01, End date: 2017-06-30
Project acronym TEBLYM
Project Teleost B lymphocytes, the equivalent of mammalian B1 innate lymphocytes?
Researcher (PI) Carolina Tafalla Piñeiro
Host Institution (HI) INSTITUTO NACIONAL DE INVESTIGACION Y TECNOLOGIA AGRARIA Y ALIMENTARIA OA MP
Call Details Starting Grant (StG), LS9, ERC-2011-StG_20101109
Summary Teleost fish are the most primitive bony vertebrates that contain immunoglobulins, although belonging to different classes than those of mammals, having only IgM, IgD and IgT. No Ig maturation to more specific class is observed in fish, providing them with an antibody response that is slow and weak in terms of antigen affinity. This is the main reason why protection conferred by disease natural resistance or vaccination does not correlate with an antibody response. Despite these great differences, fish immunologists have always thought of fish B lymphocytes as the equivalent of mammalian conventional B2 lymphocytes, thus assuming many aspects of their functionality and leaving some possibilities unexplored.
However, many evidences strongly suggest that fish B lymphocytes do not act as mammalian B2 lymphocytes but closely resemble the B1 mammalian innate lymphocytes which are known to produce large amounts of IgM without previous exposure to the pathogen in a T-independent form.
Therefore, my main objective in this proposal is the phenotypical and functional characterization of fish B cells using the rainbow trout as a model. This will be performed with no restrictions derived from the assumption of roles ascribed in the basis of their homology to mammalian B2 lymphocytes, but in the light of the hypothesis that fish B lymphocytes resemble better a B1 model. This new context will enable me to explore possible functions and characteristics previously unexplored such as T cell independence, lack of antigen engagement, poly-reactivity of antibodies produced and role in pro-inflammatory responses.
The results obtained from this project may constitute a turning point on the field of fish immunology that should redefine previous unexplained results, having also practical repercussions for future vaccination strategies. Finally, fish B lymphocytes could become a model for humans B1 cells implicated in autoimmune diseases and leukaemias.
Summary
Teleost fish are the most primitive bony vertebrates that contain immunoglobulins, although belonging to different classes than those of mammals, having only IgM, IgD and IgT. No Ig maturation to more specific class is observed in fish, providing them with an antibody response that is slow and weak in terms of antigen affinity. This is the main reason why protection conferred by disease natural resistance or vaccination does not correlate with an antibody response. Despite these great differences, fish immunologists have always thought of fish B lymphocytes as the equivalent of mammalian conventional B2 lymphocytes, thus assuming many aspects of their functionality and leaving some possibilities unexplored.
However, many evidences strongly suggest that fish B lymphocytes do not act as mammalian B2 lymphocytes but closely resemble the B1 mammalian innate lymphocytes which are known to produce large amounts of IgM without previous exposure to the pathogen in a T-independent form.
Therefore, my main objective in this proposal is the phenotypical and functional characterization of fish B cells using the rainbow trout as a model. This will be performed with no restrictions derived from the assumption of roles ascribed in the basis of their homology to mammalian B2 lymphocytes, but in the light of the hypothesis that fish B lymphocytes resemble better a B1 model. This new context will enable me to explore possible functions and characteristics previously unexplored such as T cell independence, lack of antigen engagement, poly-reactivity of antibodies produced and role in pro-inflammatory responses.
The results obtained from this project may constitute a turning point on the field of fish immunology that should redefine previous unexplained results, having also practical repercussions for future vaccination strategies. Finally, fish B lymphocytes could become a model for humans B1 cells implicated in autoimmune diseases and leukaemias.
Max ERC Funding
1 390 000 €
Duration
Start date: 2011-12-01, End date: 2016-11-30
