Project acronym BIOSUSAMIN
Project The design and development of efficient biocatalytic cascades and biosynthetic pathways for the sustainable production of amines
Researcher (PI) Francesco Mutti
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Starting Grant (StG), LS9, ERC-2014-STG
Summary The objective of this project is to design and develop biocatalytic cascades, using purified enzymes in vitro, as well as biosynthetic pathways in whole cell microbial organisms. These biocatalytic cascades and biosynthetic pathways will be developed for the synthesis of chiral and achiral amines that are of particular interest for the chemical industry. The amine functionality will be introduced using amine dehydrogenases (AmDHs) as biocatalysts in the pivotal core enzymatic step. AmDHs are a new class of enzymes that have recently been obtained by protein engineering of wild-type amino acid dehydrogenases. However, only two AmDHs have been generated so far and, moreover, they show a limited substrate scope. Therefore protein engineering will be undertaken in order to expand the substrate scope of the already existing AmDHs. In addition, novel AmDHs will be generated starting from different wild-type amino acid dehydrogenases as scaffolds, whose amino acid and DNA sequences are available in databases, literature, libraries, etc. In particular, protein engineering will be focused on the specific chemical targets that are the objectives of the designed biocatalytic cascades and in addition, screening for more diverse substrates will also be carried out. Finally, the AmDHs will be used in combination with other enzymes such as alcohol dehydrogenases, oxidases, alkane monooxygenases, etc., to deliver variously functionalised amines and derivatives as final products with elevated yields, perfect chemo- regio- and stereoselectivity, enhanced atom efficiency and minimum environmental impact. Such an approach will be realised through the design of new pathways that will convert inexpensive starting materials from renewable resources, encompassing the internal recycling of redox equivalents, the use of inorganic ammonia as nitrogen source and, if necessary, only molecular oxygen as the innocuous additional oxidant. Water will be the sole by-product.
Summary
The objective of this project is to design and develop biocatalytic cascades, using purified enzymes in vitro, as well as biosynthetic pathways in whole cell microbial organisms. These biocatalytic cascades and biosynthetic pathways will be developed for the synthesis of chiral and achiral amines that are of particular interest for the chemical industry. The amine functionality will be introduced using amine dehydrogenases (AmDHs) as biocatalysts in the pivotal core enzymatic step. AmDHs are a new class of enzymes that have recently been obtained by protein engineering of wild-type amino acid dehydrogenases. However, only two AmDHs have been generated so far and, moreover, they show a limited substrate scope. Therefore protein engineering will be undertaken in order to expand the substrate scope of the already existing AmDHs. In addition, novel AmDHs will be generated starting from different wild-type amino acid dehydrogenases as scaffolds, whose amino acid and DNA sequences are available in databases, literature, libraries, etc. In particular, protein engineering will be focused on the specific chemical targets that are the objectives of the designed biocatalytic cascades and in addition, screening for more diverse substrates will also be carried out. Finally, the AmDHs will be used in combination with other enzymes such as alcohol dehydrogenases, oxidases, alkane monooxygenases, etc., to deliver variously functionalised amines and derivatives as final products with elevated yields, perfect chemo- regio- and stereoselectivity, enhanced atom efficiency and minimum environmental impact. Such an approach will be realised through the design of new pathways that will convert inexpensive starting materials from renewable resources, encompassing the internal recycling of redox equivalents, the use of inorganic ammonia as nitrogen source and, if necessary, only molecular oxygen as the innocuous additional oxidant. Water will be the sole by-product.
Max ERC Funding
1 497 270 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym CELL HYBRIDGE
Project 3D Scaffolds as a Stem Cell Delivery System for Musculoskeletal Regenerative Medicine
Researcher (PI) Lorenzo Moroni
Host Institution (HI) UNIVERSITEIT MAASTRICHT
Call Details Starting Grant (StG), PE8, ERC-2014-STG
Summary Aging worldwide population demands new solutions to permanently restore damaged tissues, thus reducing healthcare costs. Regenerative medicine offers alternative therapies for tissue repair. Although first clinical trials revealed excellent initial response after implantation of these engineered tissues, long-term follow-ups demonstrated that degeneration and lack of integration with the surrounding tissues occur. Causes are related to insufficient cell-material interactions and loss of cell potency when cultured in two-dimensional substrates, among others.
Stem cells are a promising alternative due to their differentiation potential into multiple lineages. Yet, better control over cell-material interactions is necessary to maintain tissue engineered constructs in time. It is crucial to control stem cell quiescence, proliferation and differentiation in three-dimensional scaffolds while maintaining cells viable in situ. Stem cell activity is controlled by a complex cascade of signals called “niche”, where the extra-cellular matrix (ECM) surrounding the cells play a major role. Designing scaffolds inspired by this cellular niche and its ECM may lead to engineered tissues with instructive properties characterized by enhanced homeostasis, stability and integration with the surrounding milieu.
This research proposal aims at engineering constructs where scaffolds work as stem cell delivery systems actively controlling cell quiescence, proliferation, and differentiation. This challenge will be approached through a biomimetic design inspired by the mesenchymal stem cell niche. Three different scaffolds will be combined to achieve this purpose: (i) a scaffold designed to maintain cell quiescence; (ii) a scaffold designed to promote cell proliferation; and (iii) a scaffold designed to control cell differentiation. To prove the design criteria the evaluation of stem cell quiescence, proliferation, and differentiation will be assessed for musculoskeletal regenerative therapies.
Summary
Aging worldwide population demands new solutions to permanently restore damaged tissues, thus reducing healthcare costs. Regenerative medicine offers alternative therapies for tissue repair. Although first clinical trials revealed excellent initial response after implantation of these engineered tissues, long-term follow-ups demonstrated that degeneration and lack of integration with the surrounding tissues occur. Causes are related to insufficient cell-material interactions and loss of cell potency when cultured in two-dimensional substrates, among others.
Stem cells are a promising alternative due to their differentiation potential into multiple lineages. Yet, better control over cell-material interactions is necessary to maintain tissue engineered constructs in time. It is crucial to control stem cell quiescence, proliferation and differentiation in three-dimensional scaffolds while maintaining cells viable in situ. Stem cell activity is controlled by a complex cascade of signals called “niche”, where the extra-cellular matrix (ECM) surrounding the cells play a major role. Designing scaffolds inspired by this cellular niche and its ECM may lead to engineered tissues with instructive properties characterized by enhanced homeostasis, stability and integration with the surrounding milieu.
This research proposal aims at engineering constructs where scaffolds work as stem cell delivery systems actively controlling cell quiescence, proliferation, and differentiation. This challenge will be approached through a biomimetic design inspired by the mesenchymal stem cell niche. Three different scaffolds will be combined to achieve this purpose: (i) a scaffold designed to maintain cell quiescence; (ii) a scaffold designed to promote cell proliferation; and (iii) a scaffold designed to control cell differentiation. To prove the design criteria the evaluation of stem cell quiescence, proliferation, and differentiation will be assessed for musculoskeletal regenerative therapies.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym iTPX
Project In-cavity thermophotonic cooling
Researcher (PI) Jani Erkki Oksanen
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Call Details Starting Grant (StG), PE8, ERC-2014-STG
Summary Thermophotonic (TPX) coolers and generators based on electroluminescent (EL) cooling have the potential to enable a high efficiency replacement for thermoelectric devices. Highly optimized TPX devices can even outperform modern compressor based household refrigerators and heat pumps, enabling a significant reduction in the global energy consumption of cooling and heating. While the EL cooling phenomenon is theoretically well understood, it was only very recently demonstrated for the first time under very small power conditions. Enabling high power EL cooling, however, will require a breakthrough in reducing the losses present in conventional light emitting diodes (LED).
iTPX aims to enable this breakthrough by developing an alternative approach to enhance the efficiency of light emission. The approach is based on enclosing the emitter-absorber pair used in TPX in a single semiconductor structure forming an optical cavity. This enhances the light emission rate by an order of magnitude and provides a substantial increase in the efficiency as well as several other technical and fundamental benefits. The main goal of iTPX is to demonstrate high power EL cooling for the first time and to provide quantitative insight on the limitations and possibilities of the cavity-based approach. Recent studies have shown extremely high – over 99 % – internal and external quantum efficiencies of light emission from optically pumped semiconductor structures. This suggests that the material quality of common III-V compound semiconductors is perfectly sufficient for EL cooling if similarly performing electrically injected structures can be fabricated in the single cavity configuration.
Summary
Thermophotonic (TPX) coolers and generators based on electroluminescent (EL) cooling have the potential to enable a high efficiency replacement for thermoelectric devices. Highly optimized TPX devices can even outperform modern compressor based household refrigerators and heat pumps, enabling a significant reduction in the global energy consumption of cooling and heating. While the EL cooling phenomenon is theoretically well understood, it was only very recently demonstrated for the first time under very small power conditions. Enabling high power EL cooling, however, will require a breakthrough in reducing the losses present in conventional light emitting diodes (LED).
iTPX aims to enable this breakthrough by developing an alternative approach to enhance the efficiency of light emission. The approach is based on enclosing the emitter-absorber pair used in TPX in a single semiconductor structure forming an optical cavity. This enhances the light emission rate by an order of magnitude and provides a substantial increase in the efficiency as well as several other technical and fundamental benefits. The main goal of iTPX is to demonstrate high power EL cooling for the first time and to provide quantitative insight on the limitations and possibilities of the cavity-based approach. Recent studies have shown extremely high – over 99 % – internal and external quantum efficiencies of light emission from optically pumped semiconductor structures. This suggests that the material quality of common III-V compound semiconductors is perfectly sufficient for EL cooling if similarly performing electrically injected structures can be fabricated in the single cavity configuration.
Max ERC Funding
1 981 250 €
Duration
Start date: 2015-10-01, End date: 2020-09-30
