Project acronym bloodANDbone
Project Blood and bone – conjoined twins in health and disease: bone marrow analogs for hematological and musculoskeletal diseases
Researcher (PI) Cornelia Lee-Thedieck
Host Institution (HI) GOTTFRIED WILHELM LEIBNIZ UNIVERSITAET HANNOVER
Call Details Starting Grant (StG), LS9, ERC-2017-STG
Summary Blood and bone are closely intertwined. Their intrinsic regenerative capacities are disturbed in many hematological and musculoskeletal diseases. Re-establishing the regenerative potential is the key to cure these diseases by regenerative medicine. Multipotent stem cells of both tissues – hematopoietic stem cells (HSCs) for blood and mesenchymal stem/stromal (MSCs) for bone – are the basis for their regenerative capacity. While it is well established that HSCs are influenced by the bone marrow in their natural environment including MSCs and their progeny, surprisingly little attention has been paid to the reciprocal relationship. The hypothesis of the current proposal is that only when taking both tissues and their mutual crosstalk into account, we will be able to understand how the regenerative potential of blood and bone is impaired in disease and how it can be re-established with novel treatment strategies. For this purpose we need to understand the early events of disease onset and progression. Due to the limitations of such studies in human beings and animals, I propose to develop human in vitro models of healthy bone marrow, which can be induced to develop hematological and musculoskeletal diseases with high incidence, namely leukemia, multiple myeloma and bone metastasis. Previously my team and I developed a simplified bone marrow analog that bases on macroporous, cell-laden biomaterials with tunable physical, biochemical and biological properties. This versatility will enable us to create biomimetic human in vitro models of the human bone marrow in health and disease, which are ground-breaking in their applicability to investigate how the regenerative balance of bone marrow is maintained in health and disturbed in the different kinds of diseases – a prerequisite to develop novel regenerative treatments – as well as their scalability and thus suitability as in vitro test systems for screening of novel drugs or treatments.
Summary
Blood and bone are closely intertwined. Their intrinsic regenerative capacities are disturbed in many hematological and musculoskeletal diseases. Re-establishing the regenerative potential is the key to cure these diseases by regenerative medicine. Multipotent stem cells of both tissues – hematopoietic stem cells (HSCs) for blood and mesenchymal stem/stromal (MSCs) for bone – are the basis for their regenerative capacity. While it is well established that HSCs are influenced by the bone marrow in their natural environment including MSCs and their progeny, surprisingly little attention has been paid to the reciprocal relationship. The hypothesis of the current proposal is that only when taking both tissues and their mutual crosstalk into account, we will be able to understand how the regenerative potential of blood and bone is impaired in disease and how it can be re-established with novel treatment strategies. For this purpose we need to understand the early events of disease onset and progression. Due to the limitations of such studies in human beings and animals, I propose to develop human in vitro models of healthy bone marrow, which can be induced to develop hematological and musculoskeletal diseases with high incidence, namely leukemia, multiple myeloma and bone metastasis. Previously my team and I developed a simplified bone marrow analog that bases on macroporous, cell-laden biomaterials with tunable physical, biochemical and biological properties. This versatility will enable us to create biomimetic human in vitro models of the human bone marrow in health and disease, which are ground-breaking in their applicability to investigate how the regenerative balance of bone marrow is maintained in health and disturbed in the different kinds of diseases – a prerequisite to develop novel regenerative treatments – as well as their scalability and thus suitability as in vitro test systems for screening of novel drugs or treatments.
Max ERC Funding
1 499 920 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym conVIRgens
Project De- and reconstructing virulence strategies of fungal plant pathogens
Researcher (PI) Gunther DOEHLEMANN
Host Institution (HI) UNIVERSITAET ZU KOELN
Call Details Consolidator Grant (CoG), LS9, ERC-2017-COG
Summary Fungal pathogens are enormous threats to plants, causing tremendous losses in worldwide crop production. Mechanistic understanding of fungal virulence is crucial to developing novel plant protection strategies in sustainable agriculture.
Biotrophic pathogens colonize living plant tissue and reprogram their hosts to stimulate proliferation and development of infection structures. To promote infection, fungal pathogens secrete sets of virulence proteins termed “effectors” in a spatiotemporal program. Many economically relevant biotrophs like rusts and powdery mildew fungi are obligate pathogens. These organisms cannot be grown in culture and are not amenable to reverse genetics, which is a severe constraint for current research. In contrast, the biotrophic smut fungi have a haploid yeast stage, which allows simple cultivation and genetic modification. The causal agent of corn smut disease, Ustilago maydis, is one of the best-established model organisms for fungal genetics.
This project aims to utilize the excellent genetic accessibility of U. maydis to approach a previously impossible, pioneering enterprise: the synthetic reconstruction of eukaryotic plant pathogens. In a first step, fungal virulence will be deconstructed by consecutive deletion of the U. maydis effector repertoire to generate disarmed mutants. These strains will serve as chassis for subsequent reconstruction of fungal pathogenicity from different sources. A combination of transcriptomics and comparative genomics will help to define synthetic effector modules to reconstruct virulence in the chassis strains.
Deconstruction of U. maydis virulence will identify a complete arsenal of fungal virulence factors. Reconstruction of virulence will show how effector modules determine fungal virulence, including those of the previously not accessible obligate biotrophs. conVIRgens will thereby provide fundamentally new insights and novel functional tools towards the understanding of microbial virulence.
Summary
Fungal pathogens are enormous threats to plants, causing tremendous losses in worldwide crop production. Mechanistic understanding of fungal virulence is crucial to developing novel plant protection strategies in sustainable agriculture.
Biotrophic pathogens colonize living plant tissue and reprogram their hosts to stimulate proliferation and development of infection structures. To promote infection, fungal pathogens secrete sets of virulence proteins termed “effectors” in a spatiotemporal program. Many economically relevant biotrophs like rusts and powdery mildew fungi are obligate pathogens. These organisms cannot be grown in culture and are not amenable to reverse genetics, which is a severe constraint for current research. In contrast, the biotrophic smut fungi have a haploid yeast stage, which allows simple cultivation and genetic modification. The causal agent of corn smut disease, Ustilago maydis, is one of the best-established model organisms for fungal genetics.
This project aims to utilize the excellent genetic accessibility of U. maydis to approach a previously impossible, pioneering enterprise: the synthetic reconstruction of eukaryotic plant pathogens. In a first step, fungal virulence will be deconstructed by consecutive deletion of the U. maydis effector repertoire to generate disarmed mutants. These strains will serve as chassis for subsequent reconstruction of fungal pathogenicity from different sources. A combination of transcriptomics and comparative genomics will help to define synthetic effector modules to reconstruct virulence in the chassis strains.
Deconstruction of U. maydis virulence will identify a complete arsenal of fungal virulence factors. Reconstruction of virulence will show how effector modules determine fungal virulence, including those of the previously not accessible obligate biotrophs. conVIRgens will thereby provide fundamentally new insights and novel functional tools towards the understanding of microbial virulence.
Max ERC Funding
1 922 000 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym LightZymes
Project Evolution of artificial enzymes for light-driven reactions by implementing unnatural cofactors in protein scaffolds
Researcher (PI) Matthias HÖHNE
Host Institution (HI) UNIVERSITAET GREIFSWALD
Call Details Starting Grant (StG), LS9, ERC-2017-STG
Summary The LightZymes project aims to create artificial enzymes (LightZymes) catalyzing selective light-driven conversions of small organic molecules.
Enzyme catalysis has a large potential in the development of a sustainable, bio-based economy and is increasingly applied on industrial scale. Nature’s repertoire of enzymatic reactions is huge, but for many reactions developed by chemists, no natural enzyme is available.
I envision expanding the chemical diversity of enzymes to photoredox catalysis. Chemists perform this type of reactions by employing photo(organo) redox catalysts (PC). However, achieving regio- and stereoselectivities is challenging, because radical intermediates generated during the reaction are difficult to control. To solve this problem, I will combine the strength of bio- and photocatalysis: organic PCs as artificial cofactors provide new reactivities, and the proteins will be evolved to render the reactions highly selective. This approach differs from artificial photosynthesis: instead converting light energy in high-energy cofactors (NADPH, ATP), light will directly enable selective synthesis reactions.
Efficient directed evolution requires an easy assembly of the catalyst, preferentially inside the cell. I propose to apply genetic code engineering and to supply the PC in the form of non-canonical amino acids (ncAA). Engineered amino acyl tRNA synthetases will incorporate the PC directly during ribosomal synthesis. This will facilitate–for the first time–the assembly of hybrid catalysts in the cytoplasm without needing further modifications or purifications. This opens the door for applying high-throughput screening based on mass spectrometry and FACS to generate highly selective variants.
By bridging the concepts of photoorganocatalysis and biocatalysis, LightZymes will substantially expand the chemical repertoire of naturally evolved enzymes. This paves the way to directly using light as energy source to drive biocatalytic asymmetric reactions.
Summary
The LightZymes project aims to create artificial enzymes (LightZymes) catalyzing selective light-driven conversions of small organic molecules.
Enzyme catalysis has a large potential in the development of a sustainable, bio-based economy and is increasingly applied on industrial scale. Nature’s repertoire of enzymatic reactions is huge, but for many reactions developed by chemists, no natural enzyme is available.
I envision expanding the chemical diversity of enzymes to photoredox catalysis. Chemists perform this type of reactions by employing photo(organo) redox catalysts (PC). However, achieving regio- and stereoselectivities is challenging, because radical intermediates generated during the reaction are difficult to control. To solve this problem, I will combine the strength of bio- and photocatalysis: organic PCs as artificial cofactors provide new reactivities, and the proteins will be evolved to render the reactions highly selective. This approach differs from artificial photosynthesis: instead converting light energy in high-energy cofactors (NADPH, ATP), light will directly enable selective synthesis reactions.
Efficient directed evolution requires an easy assembly of the catalyst, preferentially inside the cell. I propose to apply genetic code engineering and to supply the PC in the form of non-canonical amino acids (ncAA). Engineered amino acyl tRNA synthetases will incorporate the PC directly during ribosomal synthesis. This will facilitate–for the first time–the assembly of hybrid catalysts in the cytoplasm without needing further modifications or purifications. This opens the door for applying high-throughput screening based on mass spectrometry and FACS to generate highly selective variants.
By bridging the concepts of photoorganocatalysis and biocatalysis, LightZymes will substantially expand the chemical repertoire of naturally evolved enzymes. This paves the way to directly using light as energy source to drive biocatalytic asymmetric reactions.
Max ERC Funding
1 498 749 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym MaCChines
Project Molecular machines based on coiled-coil protein origami
Researcher (PI) Roman JERALA
Host Institution (HI) KEMIJSKI INSTITUT
Call Details Advanced Grant (AdG), LS9, ERC-2017-ADG
Summary Proteins are the most versatile and complex smart nanomaterials, forming molecular machines and performing numerous functions from structure building, recognition, catalysis to locomotion. Nature however explored only a tiny fraction of possible protein sequences and structures. Design of proteins with new, in nature unseen shapes and features, offers high rewards for medicine, technology and science. In 2013 my group pioneered the design of a new type of modular coiled-coil protein origami (CCPO) folds. This type of de novo designed proteins are defined by the sequence of coiled-coil (CC) dimer-forming modules that are concatenated by flexible linkers into a single polypeptide chain that self-assembles into a polyhedral cage based on pairwise CC interactions. This is in contrast to naturally evolved proteins where their fold is defined by a compact hydrophobic core. We recently demonstrated the robustness of this strategy by the largest de novo designed single chain protein, construction of tetrahedral, pyramid, trigonal prism and bipyramid cages that self-assemble in vivo.
This proposal builds on unique advantages of CCPOs and represents a new frontier of this branch of protein design science. I propose to introduce functional domains into selected positions of CCPO cages, implement new types of building modules that will enable regulated CCPO assembly and disassembly, test new strategies of caging and release of cargo molecules for targeted delivery, design knotted and crosslinked protein cages and introduce toehold displacement for the regulated structural rearrangement of CCPOs required for designed molecular machines, which will be demonstrated on protein nanotweezers. Technology for the positional combinatorial library-based single pot assembly of CCPO genes will provide high throughput of CCPO variants. Project will result in new methodology, understanding of potentials of CCPOs for designed molecular machines and in demonstration of different applications.
Summary
Proteins are the most versatile and complex smart nanomaterials, forming molecular machines and performing numerous functions from structure building, recognition, catalysis to locomotion. Nature however explored only a tiny fraction of possible protein sequences and structures. Design of proteins with new, in nature unseen shapes and features, offers high rewards for medicine, technology and science. In 2013 my group pioneered the design of a new type of modular coiled-coil protein origami (CCPO) folds. This type of de novo designed proteins are defined by the sequence of coiled-coil (CC) dimer-forming modules that are concatenated by flexible linkers into a single polypeptide chain that self-assembles into a polyhedral cage based on pairwise CC interactions. This is in contrast to naturally evolved proteins where their fold is defined by a compact hydrophobic core. We recently demonstrated the robustness of this strategy by the largest de novo designed single chain protein, construction of tetrahedral, pyramid, trigonal prism and bipyramid cages that self-assemble in vivo.
This proposal builds on unique advantages of CCPOs and represents a new frontier of this branch of protein design science. I propose to introduce functional domains into selected positions of CCPO cages, implement new types of building modules that will enable regulated CCPO assembly and disassembly, test new strategies of caging and release of cargo molecules for targeted delivery, design knotted and crosslinked protein cages and introduce toehold displacement for the regulated structural rearrangement of CCPOs required for designed molecular machines, which will be demonstrated on protein nanotweezers. Technology for the positional combinatorial library-based single pot assembly of CCPO genes will provide high throughput of CCPO variants. Project will result in new methodology, understanding of potentials of CCPOs for designed molecular machines and in demonstration of different applications.
Max ERC Funding
2 497 125 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym MedPlant
Project Harnessing the Molecules of Medicinal Plants
Researcher (PI) Sarah OCONNOR
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), LS9, ERC-2017-ADG
Summary Plants, as sessile organisms, synthesize complex molecules for defense and signaling. Humans have long exploited the potent medicinal activities of these plant natural products: artemisinin from sweet wormwood is used to cure malaria, vincristine from Madagascar periwinkle is used to treat cancer, and morphine from poppy alleviates pain. Synthetic biology approaches are being used with increasing success to overproduce these expensive molecules, which are often present at low levels in the plant. However, to pursue such approaches effectively, we must fully understand the biosynthetic pathways that generate these molecules. This pathway discovery process has been a major bottleneck in harnessing the chemical power of plants.
Recent advances in sequencing, bioinformatics and metabolomics have provided the tools to address plant natural product metabolism on an unprecedented scale: we can now use inexpensive RNA-seq data, in combination with bioinformatic analyses and metabolomic data, for rapid identification of pathway-specific biosynthetic gene candidates.
Here we use these advances, along with our expertise in chemistry, to unlock the extraordinary chemical diversity that is found within the ca. 3000 members of the plant-derived monoterpene indole alkaloid metabolites. By strategically selecting a group of molecules that are chemically diverse, yet biosynthetically and evolutionarily related, the gene discovery process will be dramatically accelerated (Objective 1). Moreover, using this strategy, we will uncover new biochemical mechanisms by which chemical diversity is generated in plants (Objective 2). Understanding these mechanisms will allow us to generate “unnatural” chemical diversity in the laboratory by creating production platforms that produce new-to-nature molecules that may potentially have important applications (Objective 3).
Summary
Plants, as sessile organisms, synthesize complex molecules for defense and signaling. Humans have long exploited the potent medicinal activities of these plant natural products: artemisinin from sweet wormwood is used to cure malaria, vincristine from Madagascar periwinkle is used to treat cancer, and morphine from poppy alleviates pain. Synthetic biology approaches are being used with increasing success to overproduce these expensive molecules, which are often present at low levels in the plant. However, to pursue such approaches effectively, we must fully understand the biosynthetic pathways that generate these molecules. This pathway discovery process has been a major bottleneck in harnessing the chemical power of plants.
Recent advances in sequencing, bioinformatics and metabolomics have provided the tools to address plant natural product metabolism on an unprecedented scale: we can now use inexpensive RNA-seq data, in combination with bioinformatic analyses and metabolomic data, for rapid identification of pathway-specific biosynthetic gene candidates.
Here we use these advances, along with our expertise in chemistry, to unlock the extraordinary chemical diversity that is found within the ca. 3000 members of the plant-derived monoterpene indole alkaloid metabolites. By strategically selecting a group of molecules that are chemically diverse, yet biosynthetically and evolutionarily related, the gene discovery process will be dramatically accelerated (Objective 1). Moreover, using this strategy, we will uncover new biochemical mechanisms by which chemical diversity is generated in plants (Objective 2). Understanding these mechanisms will allow us to generate “unnatural” chemical diversity in the laboratory by creating production platforms that produce new-to-nature molecules that may potentially have important applications (Objective 3).
Max ERC Funding
2 499 999 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym PRO_PHAGE
Project Impact and interaction of prophage elements in bacterial host strains of biotechnological relevance
Researcher (PI) Julia FRUNZKE
Host Institution (HI) FORSCHUNGSZENTRUM JULICH GMBH
Call Details Starting Grant (StG), LS9, ERC-2017-STG
Summary Phages, viruses that prey on bacteria, are the most abundant and diverse inhabitants of the Earth. Temperate bacteriophages are able to integrate into the host genome and maintain as prophages a long-term association with their host. Illustrated by the development of mutually beneficial traits, this close interaction between host and virus has significantly shaped bacterial evolution. However, the immense genetic resources of phage genomes still remain almost unexplored. For the transition to a sustainable bioeconomy, we strongly depend on microbes as hosts for the production of value-added compounds. PRO_PHAGE will exploit recent advances in next-generation sequencing (NGS), single-cell analysis, and high-throughput (HT) phenotyping to evaluate the impact of phage elements on host fitness and to use this knowledge for the improvement of future metabolic engineering approaches.
By combining an explorative approach with subsequent molecular analysis of selected targets, PRO_PHAGE will deliver novel insights into this genetic resource and will reveal the risks and potential for metabolic engineering by pursuing four major objectives. 1) Based on a comprehensive bioinformatic analysis, the impact of phage elements will be studied by HT phenotyping of selected strains. 2) The regulatory interaction of phage and host will be analysed by focusing on host-encoded xenogeneic silencing proteins and their role in the integration of foreign DNA. 3) The spontaneous activation of phage elements will be studied at the genomic scale to decipher molecular triggers and their impact on host gene expression. For this purpose, a novel workflow combining fluorescence-activated cell sorting and NGS will be developed, which will be broadly applicable for studying microbial population dynamics at unprecedented resolution. 4) Finally, the insights obtained will be benchmarked for metabolic engineering approaches in order to generate robust and flexible chassis strains for industrial product
Summary
Phages, viruses that prey on bacteria, are the most abundant and diverse inhabitants of the Earth. Temperate bacteriophages are able to integrate into the host genome and maintain as prophages a long-term association with their host. Illustrated by the development of mutually beneficial traits, this close interaction between host and virus has significantly shaped bacterial evolution. However, the immense genetic resources of phage genomes still remain almost unexplored. For the transition to a sustainable bioeconomy, we strongly depend on microbes as hosts for the production of value-added compounds. PRO_PHAGE will exploit recent advances in next-generation sequencing (NGS), single-cell analysis, and high-throughput (HT) phenotyping to evaluate the impact of phage elements on host fitness and to use this knowledge for the improvement of future metabolic engineering approaches.
By combining an explorative approach with subsequent molecular analysis of selected targets, PRO_PHAGE will deliver novel insights into this genetic resource and will reveal the risks and potential for metabolic engineering by pursuing four major objectives. 1) Based on a comprehensive bioinformatic analysis, the impact of phage elements will be studied by HT phenotyping of selected strains. 2) The regulatory interaction of phage and host will be analysed by focusing on host-encoded xenogeneic silencing proteins and their role in the integration of foreign DNA. 3) The spontaneous activation of phage elements will be studied at the genomic scale to decipher molecular triggers and their impact on host gene expression. For this purpose, a novel workflow combining fluorescence-activated cell sorting and NGS will be developed, which will be broadly applicable for studying microbial population dynamics at unprecedented resolution. 4) Finally, the insights obtained will be benchmarked for metabolic engineering approaches in order to generate robust and flexible chassis strains for industrial product
Max ERC Funding
1 482 672 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym RNActivate
Project Optochemical control of cell fate by activation of mRNA translation
Researcher (PI) Andrea RENTMEISTER
Host Institution (HI) WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER
Call Details Consolidator Grant (CoG), LS9, ERC-2017-COG
Summary Light is an excellent external regulatory element that can be applied to cells and organisms with high spatio-temporal precision and without interfering with cellular processes. Optochemical biology exploits small photo-responsive chemical groups to cage and activate or to switch biomolecular functions in response to light of a defined wavelength. Caged antisense agents have enabled down-regulation of gene expression with spatio-temporal control at the messenger-RNA (mRNA) level in vivo, however approaches for triggering translation of exogenous mRNA lack efficient turn-on effects. To explore the effects of conditional and transient ectopic gene expression in a developing organism it is vital to fully abrogate and restore translational efficiency.
The goal of this project is to bring eukaryotic mRNA under the control of light to trigger efficient ectopic translation with spatio-temporal resolution in cells and in vivo. To achieve this, eukaryotic mRNA will be photo-caged at its 5′ cap using a highly promiscuous methyltransferase capable of transferring very bulky moieties from synthetic analogs of the cosubstrate S-adenosylmethionine (AdoMet). A single 5′ cap modification will block translation of the respective mRNA. Its light-triggered removal will release unmodified capped RNA, which in cells will be efficiently remethylated to form the canonical 5′ cap resulting in uncompromised translation.
In addition to labeling and tracking subpopulations of cells, we will use our technology to control and to manipulate cell fate by locally producing proteins responsible for cell death, genome engineering, and cell migration. We will use cultured cells and one-cell stage zebrafish embryos that can be easily injected with mRNA to study the function of ectopic gene expression in early development. Our approach will overcome current limitations of photo-inducible mRNA translation and enable us to manipulate a developing organism at the molecular level.
Summary
Light is an excellent external regulatory element that can be applied to cells and organisms with high spatio-temporal precision and without interfering with cellular processes. Optochemical biology exploits small photo-responsive chemical groups to cage and activate or to switch biomolecular functions in response to light of a defined wavelength. Caged antisense agents have enabled down-regulation of gene expression with spatio-temporal control at the messenger-RNA (mRNA) level in vivo, however approaches for triggering translation of exogenous mRNA lack efficient turn-on effects. To explore the effects of conditional and transient ectopic gene expression in a developing organism it is vital to fully abrogate and restore translational efficiency.
The goal of this project is to bring eukaryotic mRNA under the control of light to trigger efficient ectopic translation with spatio-temporal resolution in cells and in vivo. To achieve this, eukaryotic mRNA will be photo-caged at its 5′ cap using a highly promiscuous methyltransferase capable of transferring very bulky moieties from synthetic analogs of the cosubstrate S-adenosylmethionine (AdoMet). A single 5′ cap modification will block translation of the respective mRNA. Its light-triggered removal will release unmodified capped RNA, which in cells will be efficiently remethylated to form the canonical 5′ cap resulting in uncompromised translation.
In addition to labeling and tracking subpopulations of cells, we will use our technology to control and to manipulate cell fate by locally producing proteins responsible for cell death, genome engineering, and cell migration. We will use cultured cells and one-cell stage zebrafish embryos that can be easily injected with mRNA to study the function of ectopic gene expression in early development. Our approach will overcome current limitations of photo-inducible mRNA translation and enable us to manipulate a developing organism at the molecular level.
Max ERC Funding
1 990 225 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym YEAST-TRANS
Project Deciphering the transport mechanisms of small xenobiotic molecules in synthetic yeast cell factories
Researcher (PI) Irina BORODINA
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Starting Grant (StG), LS9, ERC-2017-STG
Summary Industrial biotechnology employs synthetic cell factories to create bulk and fine chemicals and fuels from renewable resources, laying the basis for the future bio-based economy. The major part of the wanted bio-based chemicals are not native to the host cell, such as yeast, i.e. they are xenobiotic. Some xenobiotic compounds are readily secreted by synthetic cells, some are poorly secreted and some are not secreted at all, but how does this transport occur? Or why does it not occur? These fundamental questions remain to be answered and this will have great implications on industrial biotechnology, because improved secretion would bring down the production costs and enable the emergence of novel bio-based products.
YEAST-TRANS will fill in this knowledge gap by carrying out the first systematic genome-scale transporter study to uncover the transport mechanisms of small xenobiotic molecules by synthetic yeast cells and to apply this knowledge for engineering more efficient cell factories for bio-based production of fuels and chemicals.
Summary
Industrial biotechnology employs synthetic cell factories to create bulk and fine chemicals and fuels from renewable resources, laying the basis for the future bio-based economy. The major part of the wanted bio-based chemicals are not native to the host cell, such as yeast, i.e. they are xenobiotic. Some xenobiotic compounds are readily secreted by synthetic cells, some are poorly secreted and some are not secreted at all, but how does this transport occur? Or why does it not occur? These fundamental questions remain to be answered and this will have great implications on industrial biotechnology, because improved secretion would bring down the production costs and enable the emergence of novel bio-based products.
YEAST-TRANS will fill in this knowledge gap by carrying out the first systematic genome-scale transporter study to uncover the transport mechanisms of small xenobiotic molecules by synthetic yeast cells and to apply this knowledge for engineering more efficient cell factories for bio-based production of fuels and chemicals.
Max ERC Funding
1 423 358 €
Duration
Start date: 2017-12-01, End date: 2022-11-30
