Project acronym ABEL
Project "Alpha-helical Barrels: Exploring, Understanding and Exploiting a New Class of Protein Structure"
Researcher (PI) Derek Neil Woolfson
Host Institution (HI) UNIVERSITY OF BRISTOL
Call Details Advanced Grant (AdG), LS9, ERC-2013-ADG
Summary "Recently through de novo peptide design, we have discovered and presented a new protein structure. This is an all-parallel, 6-helix bundle with a continuous central channel of 0.5 – 0.6 nm diameter. We posit that this is one of a broader class of protein structures that we call the alpha-helical barrels. Here, in three Work Packages, we propose to explore these structures and to develop protein functions within them. First, through a combination of computer-aided design, peptide synthesis and thorough biophysical characterization, we will examine the extents and limits of the alpha-helical-barrel structures. Whilst this is curiosity driven research, it also has practical consequences for the studies that will follow; that is, alpha-helical barrels made from increasing numbers of helices have channels or pores that increase in a predictable way. Second, we will use rational and empirical design approaches to engineer a range of functions within these cavities, including binding capabilities and enzyme-like activities. Finally, and taking the programme into another ambitious area, we will use the alpha-helical barrels to template other folds that are otherwise difficult to design and engineer, notably beta-barrels that insert into membranes to render ion-channel and sensor functions."
Summary
"Recently through de novo peptide design, we have discovered and presented a new protein structure. This is an all-parallel, 6-helix bundle with a continuous central channel of 0.5 – 0.6 nm diameter. We posit that this is one of a broader class of protein structures that we call the alpha-helical barrels. Here, in three Work Packages, we propose to explore these structures and to develop protein functions within them. First, through a combination of computer-aided design, peptide synthesis and thorough biophysical characterization, we will examine the extents and limits of the alpha-helical-barrel structures. Whilst this is curiosity driven research, it also has practical consequences for the studies that will follow; that is, alpha-helical barrels made from increasing numbers of helices have channels or pores that increase in a predictable way. Second, we will use rational and empirical design approaches to engineer a range of functions within these cavities, including binding capabilities and enzyme-like activities. Finally, and taking the programme into another ambitious area, we will use the alpha-helical barrels to template other folds that are otherwise difficult to design and engineer, notably beta-barrels that insert into membranes to render ion-channel and sensor functions."
Max ERC Funding
2 467 844 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym ACETOGENS
Project Acetogenic bacteria: from basic physiology via gene regulation to application in industrial biotechnology
Researcher (PI) Volker MÜLLER
Host Institution (HI) JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN
Call Details Advanced Grant (AdG), LS9, ERC-2016-ADG
Summary Demand for biofuels and other biologically derived commodities is growing worldwide as efforts increase to reduce reliance on fossil fuels and to limit climate change. Most commercial approaches rely on fermentations of organic matter with its inherent problems in producing CO2 and being in conflict with the food supply of humans. These problems are avoided if CO2 can be used as feedstock. Autotrophic organisms can fix CO2 by producing chemicals that are used as building blocks for the synthesis of cellular components (Biomass). Acetate-forming bacteria (acetogens) do neither require light nor oxygen for this and they can be used in bioreactors to reduce CO2 with hydrogen gas, carbon monoxide or an organic substrate. Gas fermentation using these bacteria has already been realized on an industrial level in two pre-commercial 100,000 gal/yr demonstration facilities to produce fuel ethanol from abundant waste gas resources (by LanzaTech). Acetogens can metabolise a wide variety of substrates that could be used for the production of biocommodities. However, their broad use to produce biofuels and platform chemicals from substrates other than gases or together with gases is hampered by our very limited knowledge about their metabolism and ability to use different substrates simultaneously. Nearly nothing is known about regulatory processes involved in substrate utilization or product formation but this is an absolute requirement for metabolic engineering approaches. The aim of this project is to provide this basic knowledge about metabolic routes in the acetogenic model strain Acetobacterium woodii and their regulation. We will unravel the function of “organelles” found in this bacterium and explore their potential as bio-nanoreactors for the production of biocommodities and pave the road for the industrial use of A. woodii in energy (hydrogen) storage. Thus, this project creates cutting-edge opportunities for the development of biosustainable technologies in Europe.
Summary
Demand for biofuels and other biologically derived commodities is growing worldwide as efforts increase to reduce reliance on fossil fuels and to limit climate change. Most commercial approaches rely on fermentations of organic matter with its inherent problems in producing CO2 and being in conflict with the food supply of humans. These problems are avoided if CO2 can be used as feedstock. Autotrophic organisms can fix CO2 by producing chemicals that are used as building blocks for the synthesis of cellular components (Biomass). Acetate-forming bacteria (acetogens) do neither require light nor oxygen for this and they can be used in bioreactors to reduce CO2 with hydrogen gas, carbon monoxide or an organic substrate. Gas fermentation using these bacteria has already been realized on an industrial level in two pre-commercial 100,000 gal/yr demonstration facilities to produce fuel ethanol from abundant waste gas resources (by LanzaTech). Acetogens can metabolise a wide variety of substrates that could be used for the production of biocommodities. However, their broad use to produce biofuels and platform chemicals from substrates other than gases or together with gases is hampered by our very limited knowledge about their metabolism and ability to use different substrates simultaneously. Nearly nothing is known about regulatory processes involved in substrate utilization or product formation but this is an absolute requirement for metabolic engineering approaches. The aim of this project is to provide this basic knowledge about metabolic routes in the acetogenic model strain Acetobacterium woodii and their regulation. We will unravel the function of “organelles” found in this bacterium and explore their potential as bio-nanoreactors for the production of biocommodities and pave the road for the industrial use of A. woodii in energy (hydrogen) storage. Thus, this project creates cutting-edge opportunities for the development of biosustainable technologies in Europe.
Max ERC Funding
2 497 140 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym ADREEM
Project Adding Another Dimension – Arrays of 3D Bio-Responsive Materials
Researcher (PI) Mark Bradley
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Call Details Advanced Grant (AdG), LS9, ERC-2013-ADG
Summary This proposal is focused in the areas of chemical medicine and chemical biology with the key drivers being the discovery and development of new materials that have practical functionality and application. The project will enable the fabrication of thousands of three-dimensional “smart-polymers” that will allow: (i). The precise and controlled release of drugs upon the addition of either a small molecule trigger or in response to disease, (ii). The discovery of materials that control and manipulate cells with the identification of scaffolds that provide the necessary biochemical cues for directing cell fate and drive tissue regeneration and (iii). The development of new classes of “smart-polymers” able, in real-time, to sense and report bacterial contamination. The newly discovered materials will find multiple biomedical applications in regenerative medicine and biotechnology ranging from 3D cell culture, bone repair and niche stabilisation to bacterial sensing/removal, while offering a new paradigm in drug delivery with biomarker triggered drug release.
Summary
This proposal is focused in the areas of chemical medicine and chemical biology with the key drivers being the discovery and development of new materials that have practical functionality and application. The project will enable the fabrication of thousands of three-dimensional “smart-polymers” that will allow: (i). The precise and controlled release of drugs upon the addition of either a small molecule trigger or in response to disease, (ii). The discovery of materials that control and manipulate cells with the identification of scaffolds that provide the necessary biochemical cues for directing cell fate and drive tissue regeneration and (iii). The development of new classes of “smart-polymers” able, in real-time, to sense and report bacterial contamination. The newly discovered materials will find multiple biomedical applications in regenerative medicine and biotechnology ranging from 3D cell culture, bone repair and niche stabilisation to bacterial sensing/removal, while offering a new paradigm in drug delivery with biomarker triggered drug release.
Max ERC Funding
2 310 884 €
Duration
Start date: 2014-11-01, End date: 2019-10-31
Project acronym AGRISCENTS
Project Scents and sensibility in agriculture: exploiting specificity in herbivore- and pathogen-induced plant volatiles for real-time crop monitoring
Researcher (PI) Theodoor Turlings
Host Institution (HI) UNIVERSITE DE NEUCHATEL
Call Details Advanced Grant (AdG), LS9, ERC-2017-ADG
Summary Plants typically release large quantities of volatiles in response to attack by herbivores or pathogens. I may claim to have contributed to various breakthroughs in this research field, including the discovery that the volatile blends induced by different attackers are astonishingly specific, resulting in characteristic, readily distinguishable odour blends. Using maize as our model plant, I wish to take several leaps forward in our understanding of this signal specificity and use this knowledge to develop sensors for the real-time detection of crop pests and diseases. For this, three interconnected work-packages will aim to:
• Develop chemical analytical techniques and statistical models to decipher the odorous vocabulary of plants, and to create a complete inventory of “odour-prints” for a wide range of herbivore-plant and pathogen-plant combinations, including simultaneous infestations.
• Develop and optimize nano-mechanical sensors for the detection of specific plant volatile mixtures. For this, we will initially adapt a prototype sensor that has been successfully developed for the detection of cancer-related volatiles in human breath.
• Genetically manipulate maize plants to release a unique blend of root-produced volatiles upon herbivory. For this, we will engineer gene cassettes that combine recently identified P450 (CYP) genes from poplar with inducible, root-specific promoters from maize. This will result in maize plants that, in response to pest attack, release easy-to-detect aldoximes and nitriles from their roots.
In short, by investigating and manipulating the specificity of inducible odour blends we will generate the necessary knowhow to develop a novel odour-detection device. The envisioned sensor technology will permit real-time monitoring of the pests and enable farmers to apply crop protection treatments at the right time and in the right place.
Summary
Plants typically release large quantities of volatiles in response to attack by herbivores or pathogens. I may claim to have contributed to various breakthroughs in this research field, including the discovery that the volatile blends induced by different attackers are astonishingly specific, resulting in characteristic, readily distinguishable odour blends. Using maize as our model plant, I wish to take several leaps forward in our understanding of this signal specificity and use this knowledge to develop sensors for the real-time detection of crop pests and diseases. For this, three interconnected work-packages will aim to:
• Develop chemical analytical techniques and statistical models to decipher the odorous vocabulary of plants, and to create a complete inventory of “odour-prints” for a wide range of herbivore-plant and pathogen-plant combinations, including simultaneous infestations.
• Develop and optimize nano-mechanical sensors for the detection of specific plant volatile mixtures. For this, we will initially adapt a prototype sensor that has been successfully developed for the detection of cancer-related volatiles in human breath.
• Genetically manipulate maize plants to release a unique blend of root-produced volatiles upon herbivory. For this, we will engineer gene cassettes that combine recently identified P450 (CYP) genes from poplar with inducible, root-specific promoters from maize. This will result in maize plants that, in response to pest attack, release easy-to-detect aldoximes and nitriles from their roots.
In short, by investigating and manipulating the specificity of inducible odour blends we will generate the necessary knowhow to develop a novel odour-detection device. The envisioned sensor technology will permit real-time monitoring of the pests and enable farmers to apply crop protection treatments at the right time and in the right place.
Max ERC Funding
2 498 086 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym AMAIZE
Project Atlas of leaf growth regulatory networks in MAIZE
Researcher (PI) Dirk, Gustaaf Inzé
Host Institution (HI) VIB
Call Details Advanced Grant (AdG), LS9, ERC-2013-ADG
Summary "Understanding how organisms regulate size is one of the most fascinating open questions in biology. The aim of the AMAIZE project is to unravel how growth of maize leaves is controlled. Maize leaf development offers great opportunities to study the dynamics of growth regulatory networks, essentially because leaf development is a linear system with cell division at the leaf basis followed by cell expansion and maturation. Furthermore, the growth zone is relatively large allowing easy access of tissues at different positions. Four different perturbations of maize leaf size will be analyzed with cellular resolution: wild-type and plants having larger leaves (as a consequence of GA20OX1 overexpression), both grown under either well-watered or mild drought conditions. Firstly, a 3D cellular map of the growth zone of the fourth leaf will be made. RNA-SEQ of three different tissues (adaxial- and abaxial epidermis; mesophyll) obtained by laser dissection with an interval of 2.5 mm along the growth zone will allow for the analysis of the transcriptome with high resolution. Additionally, the composition of fifty selected growth regulatory protein complexes and DNA targets of transcription factors will be determined with an interval of 5 mm along the growth zone. Computational methods will be used to construct comprehensive integrative maps of the cellular and molecular processes occurring along the growth zone. Finally, selected regulatory nodes of the growth regulatory networks will be further functionally analyzed using a transactivation system in maize.
AMAIZE opens up new perspectives for the identification of optimal growth regulatory networks that can be selected for by advanced breeding or for which more robust variants (e.g. reduced susceptibility to drought) can be obtained through genetic engineering. The ability to improve the growth of maize and in analogy other cereals could have a high impact in providing food security"
Summary
"Understanding how organisms regulate size is one of the most fascinating open questions in biology. The aim of the AMAIZE project is to unravel how growth of maize leaves is controlled. Maize leaf development offers great opportunities to study the dynamics of growth regulatory networks, essentially because leaf development is a linear system with cell division at the leaf basis followed by cell expansion and maturation. Furthermore, the growth zone is relatively large allowing easy access of tissues at different positions. Four different perturbations of maize leaf size will be analyzed with cellular resolution: wild-type and plants having larger leaves (as a consequence of GA20OX1 overexpression), both grown under either well-watered or mild drought conditions. Firstly, a 3D cellular map of the growth zone of the fourth leaf will be made. RNA-SEQ of three different tissues (adaxial- and abaxial epidermis; mesophyll) obtained by laser dissection with an interval of 2.5 mm along the growth zone will allow for the analysis of the transcriptome with high resolution. Additionally, the composition of fifty selected growth regulatory protein complexes and DNA targets of transcription factors will be determined with an interval of 5 mm along the growth zone. Computational methods will be used to construct comprehensive integrative maps of the cellular and molecular processes occurring along the growth zone. Finally, selected regulatory nodes of the growth regulatory networks will be further functionally analyzed using a transactivation system in maize.
AMAIZE opens up new perspectives for the identification of optimal growth regulatory networks that can be selected for by advanced breeding or for which more robust variants (e.g. reduced susceptibility to drought) can be obtained through genetic engineering. The ability to improve the growth of maize and in analogy other cereals could have a high impact in providing food security"
Max ERC Funding
2 418 429 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym ARISYS
Project Engineering an artificial immune system with functional components assembled from prokaryotic parts and modules
Researcher (PI) Víctor De Lorenzo Prieto
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Advanced Grant (AdG), LS9, ERC-2012-ADG_20120314
Summary The objective of this project is to overcome current limitations for antibody production that are inherent to the extant immune system of vertebrates. This will be done by creating an all-in-one artificial/synthetic counterpart based exclusively on prokaryotic parts, devices and modules. To this end, ARISYS will exploit design concepts, construction hierarchies and standardization notions that stem from contemporary Synthetic Biology for the assembly and validation of (what we believe is) the most complex artificial biological system ventured thus far. This all-bacterial immune-like system will not only simplify and make affordable the manipulations necessary for antibody generation, but will also permit the application of such binders by themselves or displayed on bacterial cells to biotechnological challenges well beyond therapeutic and health-related uses. The work plan involves the assembly and validation of autonomous functional modules for [i] displaying antibody/affibody (AB) scaffolds attached to the surface of bacterial cells, [ii] conditional diversification of target-binding sequences of the ABs, [iii] contact-dependent activation of gene expression, [iv] reversible bi-stable switches, and [v] clonal selection and amplification of improved binders. These modules composed of stand-alone parts and bearing well defined input/output functions, will be assembled in the genomic chassis of streamlined Escherichia coli and Pseudomonas putida strains. The resulting molecular network will make the ABs expressed and displayed on the cell surface to proceed spontaneously (or at the user's decision) through subsequent cycles of affinity and specificity maturation towards antigens or other targets presented to the bacterial population. In this way, a single, easy-to-handle (albeit heavily engineered) strain will govern all operations that are typically scattered in a multitude of separate methods and apparatuses for AB production.
Summary
The objective of this project is to overcome current limitations for antibody production that are inherent to the extant immune system of vertebrates. This will be done by creating an all-in-one artificial/synthetic counterpart based exclusively on prokaryotic parts, devices and modules. To this end, ARISYS will exploit design concepts, construction hierarchies and standardization notions that stem from contemporary Synthetic Biology for the assembly and validation of (what we believe is) the most complex artificial biological system ventured thus far. This all-bacterial immune-like system will not only simplify and make affordable the manipulations necessary for antibody generation, but will also permit the application of such binders by themselves or displayed on bacterial cells to biotechnological challenges well beyond therapeutic and health-related uses. The work plan involves the assembly and validation of autonomous functional modules for [i] displaying antibody/affibody (AB) scaffolds attached to the surface of bacterial cells, [ii] conditional diversification of target-binding sequences of the ABs, [iii] contact-dependent activation of gene expression, [iv] reversible bi-stable switches, and [v] clonal selection and amplification of improved binders. These modules composed of stand-alone parts and bearing well defined input/output functions, will be assembled in the genomic chassis of streamlined Escherichia coli and Pseudomonas putida strains. The resulting molecular network will make the ABs expressed and displayed on the cell surface to proceed spontaneously (or at the user's decision) through subsequent cycles of affinity and specificity maturation towards antigens or other targets presented to the bacterial population. In this way, a single, easy-to-handle (albeit heavily engineered) strain will govern all operations that are typically scattered in a multitude of separate methods and apparatuses for AB production.
Max ERC Funding
2 422 271 €
Duration
Start date: 2013-05-01, End date: 2019-04-30
Project acronym BIOFORCE
Project Simultaneous multi-pathway engineering in crop plants through combinatorial genetic transformation: Creating nutritionally biofortified cereal grains for food security
Researcher (PI) Paul Christou
Host Institution (HI) UNIVERSIDAD DE LLEIDA
Call Details Advanced Grant (AdG), LS9, ERC-2008-AdG
Summary BIOFORCE has a highly ambitious applied objective: to create transgenic cereal plants that will provide a near-complete micronutrient complement (vitamins A, C, E, folate and essential minerals Ca, Fe, Se and Zn) for malnourished people in the developing world, as well as built-in resistance to insects and parasitic weeds. This in itself represents a striking advance over current efforts to address food insecurity using applied biotechnology in the developing world. We will also address fundamental mechanistic aspects of multi-gene/pathway engineering through transcriptome and metabolome profiling. Fundamental science and applied objectives will be achieved through the application of an exciting novel technology (combinatorial genetic transformation) developed and patented by my research group. This allows the simultaneous transfer of an unlimited number of transgenes into plants followed by library-based selection of plants with appropriate genotypes and phenotypes. All transgenes integrate into one locus ensuring expression stability over multiple generations. This proposal represents a new line of research in my laboratory, founded on incremental advances in the elucidation of transgene integration mechanisms in plants over the past two and a half decades. In addition to scientific issues, BIOFORCE address challenges such as intellectual property, regulatory and biosafety issues and crucially how the fruits of our work will be taken up through philanthropic initiatives in the developing world while creating exploitable opportunities elsewhere. BIOFORCE is comprehensive and it provides a complete package that stands to make an unprecedented contribution to food security in the developing world, while at the same time generating new knowledge to streamline and simplify multiplex gene transfer and the simultaneous modification of multiple complex plant metabolic pathways
Summary
BIOFORCE has a highly ambitious applied objective: to create transgenic cereal plants that will provide a near-complete micronutrient complement (vitamins A, C, E, folate and essential minerals Ca, Fe, Se and Zn) for malnourished people in the developing world, as well as built-in resistance to insects and parasitic weeds. This in itself represents a striking advance over current efforts to address food insecurity using applied biotechnology in the developing world. We will also address fundamental mechanistic aspects of multi-gene/pathway engineering through transcriptome and metabolome profiling. Fundamental science and applied objectives will be achieved through the application of an exciting novel technology (combinatorial genetic transformation) developed and patented by my research group. This allows the simultaneous transfer of an unlimited number of transgenes into plants followed by library-based selection of plants with appropriate genotypes and phenotypes. All transgenes integrate into one locus ensuring expression stability over multiple generations. This proposal represents a new line of research in my laboratory, founded on incremental advances in the elucidation of transgene integration mechanisms in plants over the past two and a half decades. In addition to scientific issues, BIOFORCE address challenges such as intellectual property, regulatory and biosafety issues and crucially how the fruits of our work will be taken up through philanthropic initiatives in the developing world while creating exploitable opportunities elsewhere. BIOFORCE is comprehensive and it provides a complete package that stands to make an unprecedented contribution to food security in the developing world, while at the same time generating new knowledge to streamline and simplify multiplex gene transfer and the simultaneous modification of multiple complex plant metabolic pathways
Max ERC Funding
2 290 046 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
Project acronym BIOMOLECULAR_COMP
Project Biomolecular computers
Researcher (PI) Ehud Shapiro
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Advanced Grant (AdG), LS9, ERC-2008-AdG
Summary Autonomous programmable computing devices made of biological molecules hold the promise of interacting with the biological environment in future biological and medical applications. Our laboratory's long-term objective is to develop a 'Doctor in a cell': molecular-sized device that can roam the body, equipped with medical knowledge. It would diagnose a disease by analyzing the data available in its biochemical environment based on the encoded medical knowledge and treat it by releasing the appropriate drug molecule in situ. This kind of device might, in the future, be delivered to all cells in a specific tissue, organ or the whole organism, and cure or kill only those cells diagnosed with a disease. Our laboratory embarked on the attempt to design and build these molecular computing devices and lay the foundation for their future biomedical applications. Several important milestones have already been accomplished towards the realization of the Doctor in a cell vision. The subject of this proposal is a construction of autonomous biomolecular computers that could be delivered into a living cell, interact with endogenous biomolecules that are known to indicate diseases, logically analyze them, make a diagnostic decision and couple it to the production of an active biomolecule capable of influencing cell fate.
Summary
Autonomous programmable computing devices made of biological molecules hold the promise of interacting with the biological environment in future biological and medical applications. Our laboratory's long-term objective is to develop a 'Doctor in a cell': molecular-sized device that can roam the body, equipped with medical knowledge. It would diagnose a disease by analyzing the data available in its biochemical environment based on the encoded medical knowledge and treat it by releasing the appropriate drug molecule in situ. This kind of device might, in the future, be delivered to all cells in a specific tissue, organ or the whole organism, and cure or kill only those cells diagnosed with a disease. Our laboratory embarked on the attempt to design and build these molecular computing devices and lay the foundation for their future biomedical applications. Several important milestones have already been accomplished towards the realization of the Doctor in a cell vision. The subject of this proposal is a construction of autonomous biomolecular computers that could be delivered into a living cell, interact with endogenous biomolecules that are known to indicate diseases, logically analyze them, make a diagnostic decision and couple it to the production of an active biomolecule capable of influencing cell fate.
Max ERC Funding
2 125 980 €
Duration
Start date: 2009-01-01, End date: 2013-10-31
Project acronym BIOSILICA
Project From gene to biomineral: Biosynthesis and application of sponge biosilica
Researcher (PI) Werner Ernst Ludwig Georg Müller
Host Institution (HI) UNIVERSITAETSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAET MAINZ
Call Details Advanced Grant (AdG), LS9, ERC-2010-AdG_20100317
Summary During the last decade, the principles of biomineralization have increasingly attracted multidisciplinary scientific attention, not only because they touch the interface between the organic/inorganic world but also because they offer fascinating bioinspired solutions to notorious problems in the fields of biotechnology and medicine. However, only one group of animals has the necessary genetic/enzymatic toolkit to control biomineralization: siliceous sponges (Porifera). Based on his pioneering discoveries in poriferan molecular biology and physiological chemistry, the PI has brought biosilicification into the focus of basic and applied research. Through multiple trendsetting approaches the molecular key components for the enzymatic synthesis of polymorphic siliceous skeletal elements in sponges have been elucidated and characterized. Subsequently, they have been employed to synthesize innovative composite materials in vitro. Nonetheless, knowledge of the functional mechanisms involved remains sketchy and harnessing biosilicification, beyond the in vitro synthesis of amorphous nanocomposites, is still impossible. Using a unique blend of cutting-edge techniques in molecular/structural biology, biochemistry, bioengineering, and material sciences, the PI approaches for the first time a comprehensive analysis of natural biomineralization, from gene to biomineral to hierarchically ordered structures of increasing complexity. The groundbreaking discoveries expected will be of extreme importance for understanding poriferan biosilicification. Concurrently, they will contribute to the development of innovative nano-biotechnological and -medical approaches that aim to elicit novel (biogenous) optical waveguide fibers and self-repairing inorganic-organic bone substitution materials.
Summary
During the last decade, the principles of biomineralization have increasingly attracted multidisciplinary scientific attention, not only because they touch the interface between the organic/inorganic world but also because they offer fascinating bioinspired solutions to notorious problems in the fields of biotechnology and medicine. However, only one group of animals has the necessary genetic/enzymatic toolkit to control biomineralization: siliceous sponges (Porifera). Based on his pioneering discoveries in poriferan molecular biology and physiological chemistry, the PI has brought biosilicification into the focus of basic and applied research. Through multiple trendsetting approaches the molecular key components for the enzymatic synthesis of polymorphic siliceous skeletal elements in sponges have been elucidated and characterized. Subsequently, they have been employed to synthesize innovative composite materials in vitro. Nonetheless, knowledge of the functional mechanisms involved remains sketchy and harnessing biosilicification, beyond the in vitro synthesis of amorphous nanocomposites, is still impossible. Using a unique blend of cutting-edge techniques in molecular/structural biology, biochemistry, bioengineering, and material sciences, the PI approaches for the first time a comprehensive analysis of natural biomineralization, from gene to biomineral to hierarchically ordered structures of increasing complexity. The groundbreaking discoveries expected will be of extreme importance for understanding poriferan biosilicification. Concurrently, they will contribute to the development of innovative nano-biotechnological and -medical approaches that aim to elicit novel (biogenous) optical waveguide fibers and self-repairing inorganic-organic bone substitution materials.
Max ERC Funding
2 183 600 €
Duration
Start date: 2011-06-01, End date: 2017-05-31
Project acronym BISON
Project Bio-Inspired Self-Assembled Supramolecular Organic Nanostructures
Researcher (PI) Ehud Gazit
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Advanced Grant (AdG), LS9, ERC-2015-AdG
Summary Peptide building blocks serve as very attractive bio-inspired elements in nanotechnology owing to their controlled self-assembly, inherent biocompatibility, chemical versatility, biological recognition abilities and facile synthesis. We have demonstrated the ability of remarkably simple aromatic peptides to form well-ordered nanostructures of exceptional physical properties. By taking inspiration from the minimal recognition modules used by nature to mediate coordinated processes of self-assembly, we have developed building blocks that form well-ordered nanostructures. The compact design of the building blocks, and therefore, the unique structural organization, resulted in metallic-like Young's modulus, blue luminescence due to quantum confinement, and notable piezoelectric properties. The goal of this proposal is to develop two new fronts for bio-inspired building block repertoire along with co-assembly to provide new avenues for organic nanotechnology. This will combine our vast experience in the assembly of aromatic peptides together with additional structural modules from nature. The new entities will be developed by exploiting the design principles of small aromatic building blocks to arrive at the smallest possible module that form super helical assembly based on the coiled coil motifs and establishing peptide nucleic acids based systems to combine the worlds of peptide and DNA nanotechnologies. The proposed research will combine extensive design and synthesis effort to provide a very diverse collection of novel buildings blocks and determination of their self-assembly process, followed by broad chemical, physical, and biological characterization of the nanostructures. Furthermore, effort will be made to establish supramolecular co-polymer systems to extend the morphological control of the assembly process. The result of the project will be a large and defined collection of novel chemical entities that will help reshape the field of bioorganic nanotechnology.
Summary
Peptide building blocks serve as very attractive bio-inspired elements in nanotechnology owing to their controlled self-assembly, inherent biocompatibility, chemical versatility, biological recognition abilities and facile synthesis. We have demonstrated the ability of remarkably simple aromatic peptides to form well-ordered nanostructures of exceptional physical properties. By taking inspiration from the minimal recognition modules used by nature to mediate coordinated processes of self-assembly, we have developed building blocks that form well-ordered nanostructures. The compact design of the building blocks, and therefore, the unique structural organization, resulted in metallic-like Young's modulus, blue luminescence due to quantum confinement, and notable piezoelectric properties. The goal of this proposal is to develop two new fronts for bio-inspired building block repertoire along with co-assembly to provide new avenues for organic nanotechnology. This will combine our vast experience in the assembly of aromatic peptides together with additional structural modules from nature. The new entities will be developed by exploiting the design principles of small aromatic building blocks to arrive at the smallest possible module that form super helical assembly based on the coiled coil motifs and establishing peptide nucleic acids based systems to combine the worlds of peptide and DNA nanotechnologies. The proposed research will combine extensive design and synthesis effort to provide a very diverse collection of novel buildings blocks and determination of their self-assembly process, followed by broad chemical, physical, and biological characterization of the nanostructures. Furthermore, effort will be made to establish supramolecular co-polymer systems to extend the morphological control of the assembly process. The result of the project will be a large and defined collection of novel chemical entities that will help reshape the field of bioorganic nanotechnology.
Max ERC Funding
3 003 125 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
