Scientific publications

2012
Synthetic gene networks as Blueprint for smart hydrogels

Kämpf, M. M. | Weber, Wilfried

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The rapidly emerging ability to design and construct synthetic gene networks in mammalian cells is based on the availability of mutually compatible genetic switches that enable the time-dependent induction of transgene expression in response to the dose of an externally applied stimulus. As these genetic switches are inherently compatible with mammalian cell physiology, they are as well predestined to control the functionality of cell-free synthetic devices within an overall physiologic background. In this chapter, we describe how a genetic switch that was originally designed for gene therapeutic studies can be applied in materials science to design and construct a biohybrid hydrogel that can be used to release a therapeutic growth factor in response to an externally applied stimulus for controlling cell fate and function in a time- and space-resolved manner. © 2012 Springer Science+Business Media, LLC.

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Methods in molecular biology,
2012, 813, 377-389.

Therapeutic synthetic gene networks

Karlsson, M. | Weber, Wilfried

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The field of synthetic biology is rapidly expanding and has over the past years evolved from the development of simple gene networks to complex treatment-oriented circuits. The reprogramming of cell fate with open-loop or closed-loop synthetic control circuits along with biologically implemented logical functions have fostered applications spanning over a wide range of disciplines, including artificial insemination, personalized medicine and the treatment of cancer and metabolic disorders. In this review we describe several applications of interactive gene networks, a synthetic biology-based approach for future gene therapy, as well as the utilization of synthetic gene circuits as blueprints for the design of stimuli-responsive biohybrid materials. The recent progress in synthetic biology, including the rewiring of biosensing devices with the body's endogenous network as well as novel therapeutic approaches originating from interdisciplinary work, generates numerous opportunities for future biomedical applications. © 2012 Elsevier Ltd.

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Current Opinion in Biotechnology,
2012, 23 (5), 703-711.

Design and construction of synthetic gene networks in mammalian cells

Karlsson, M. | Weber, Wilfried | Fussenegger, M.

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Advances in the development of molecular tools for the inducible control of transcription, translation, and protein degradation are the basis for the rapidly emerging design and construction of synthetic gene networks in mammalian cells. In this chapter, we describe such tools and how they can be integrated into a synthetic gene network with desired functionality. The network design and construction process is illustrated in the form of a detailed protocol for the implementation of a logic NOR gate based on an inducible promoter combined with an inducible protein degradation system. © 2012 Springer Science+Business Media, LLC.

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Methods in molecular biology,
2012, 813, 359-376.

Emerging biomedical applications of synthetic biology

Weber, Wilfried | Fussenegger, M.

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Synthetic biology aims to create functional devices, systems and organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. Although they were initially constructed to elucidate the dynamics of simple processes, designed devices now contribute to the understanding of disease mechanisms, provide novel diagnostic tools, enable economic production of therapeutics and allow the design of novel strategies for the treatment of cancer, immune diseases and metabolic disorders, such as diabetes and gout, as well as a range of infectious diseases. In this Review, we cover the impact and potential of synthetic biology for biomedical applications. © 2011 Macmillan Publishers Limited. All rights reserved.

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Nature Reviews Genetics,
2012, 13 (1), 21-35.

Plant and bacterial systems biology as platform for plant synthetic bio(techno)logy

Zurbriggen, M. D. | Moor, A. | Weber, Wilfried

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The recent implementation of various high-throughput biochemical and bioanalytical platforms for the study of biological systems has resulted in a wealth of experimental information that systems biology integrates into models and functional descriptions of organisms. The fast tempo of systems biology development is currently bringing in a revolution in the understanding of cell networks by providing with a holistic comprehension of cellular components and their interaction dynamics. This thorough description of biological systems has laid the grounds for the development of synthetic biology, a discipline applying basic principles of engineering for the rational assembly of biological modules into higher order complex biological systems with desired properties. Despite the success of this new field for the generation of biotechnological tools, it has not been yet widely applied to plant systems. This review aims at describing the current status of systems biology, its contribution to our understanding of plant metabolism, expression and regulatory networks and how synthetic biology approaches could benefit utilising plant and bacterial 'omics' as a source for the design and development of biological modules for the improvement of plant stress tolerance and crop production, among other applications. The article further describes synthetic biology strategies currently being applied to plant metabolic engineering, development of signalling pathways and synthetic organelles, and the potential of this new field for the understanding of plant cellular functioning and the generation of plant biotechnological tools. © 2012 Elsevier B.V..

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Journal of Biotechnology,
2012, 160 (1-2), 80-90.

Hybrid sol-gel coatings doped with transition metal ions for the protection of AA 2024-T3

Wittmar, Alexandra | Wittmar, Matthias | Ulrich, Alfred | Caparrotti, Hinka | Veith, Michael

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The protective capabilities of sol-gel coatings are determined by their physical barrier properties. For an effective protection, a homogenous crack-free material is required, which prevents from attacks of corrosive species. When the coating is damaged, active corrosion protection is usually achieved by the use of inhibitors. Among the different inhibitors rare earth ions and especially cerium have shown effective inhibiting properties. Due to the complexity of the corrosion processes, a combination of inhibitors is expected to be superior to a monocomponent inhibiting. The aim of this study was to prove which other ions, used in combination with cerium, can improve the corrosion protection abilities of hybrid silica based inorganic-organic sol-gel coatings applied on aluminium alloy 2024 substrates. Mixtures of cerium nitrate with two other potential inhibitor substances were incorporated into a sol-gel matrix and their behaviour in neutral salt spray test and during EIS measurements was investigated. The Ce–P–Pr inhibitor combination (Ce3+, PO43−, Pr3+) has shown the best long-term corrosion protection properties at low doping levels.

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Journal of Sol-Gel Science and Technology,
2012, 61 (3), 600-612.

Simple preparation routes for corrosion protection hybrid sol-gel coatings on AA 2024

Wittmar, Alexandra | Caparrotti, Hinka | Wittmar, Matthias | Veith, Michael

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In recent years, many hybrid inorganic-organic systems have been proposed in order to replace the traditional conversion coatings on metals like aluminum, and some results have been promising. However, many proposed solutions are based on complicated processes which are not easy to be adapted to industrial scale. The aim of this study was to establish a simple process leading to the production of highly efficient corrosion protective hybrid sol-gel coating systems for the aluminum alloys as replacement for the highly hazardous conventional chromate conversion coatings. Hybrid coatings have been realized by means of the sol-gel process. CeO2 and ZnO have been introduced as dispersions of nanoparticles in the system and used as corrosion inhibitors. The aim of this work was to obtain pore-free coatings with increased barrier properties using nanoparticles that possess the double function of pore fillers and corrosion inhibitors. The proposed processes led to coating materials with good adherence to the aluminum substrate and an extremely long life in the accelerated neutral salt spray test according to DIN ISO 9227. Electrochemical impedance spectroscopy approves these results by high impedance values in the low-frequency region of the Bode plot.

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Surface and Interface Analysis,
2012, 44 (1), 70-77.

Neue molekulare Indium-Zinn-Sauerstoff- und Indium-Zinn-Natrium-Sauerstoff-Chlor-Cluster

Veith, Michael | Summa, Daniela Reinhilde | Huch, Volker

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The five-membered heteroelement cluster THF·Cl2In(OtBu)3Sn reacts with the sodium stannate [Na(OtBu)3Sn]2 to produce either the new oxo-centered alkoxo cluster ClInO[Sn(OtBu)2]3 (1) (in low yield) or the heteroleptic alkoxo cluster Sn(OtBu)3InCl3Na[Sn(OtBu)2]2 (2). X-ray diffraction analyses reveal that in compound 1 the polycyclic entity is made of three tin atoms which together with a central oxygen atom form a trigonal, almost planar triangle, perpendicular to which a further indium atom is connected through the oxygen atom. The metal atoms thus are arranged in a Sn3In pyramid, the edges of which are all saturated by bridging tert-butoxy groups. The indium atom has a further chloride ligand. Compound 2 has two trigonal bipyramids as building blocks which are fused together at a six coordinate indium atom. One of the bipyramids is of the type SnO3In with tert-butyl groups on the oxygen atoms, while the other has the composition InCl3Na with chlorine atoms connecting the two metals. The sodium atom in 2 has further contacts to two plus one alkoxide groups which are part of a[Sn(OtBu)2]2 dimer disposing of a Sn2O2 central cycle. The hetero element cluster in 2 thus combines three closed entities and its skeleton SnO3InCl3NaO2Sn2O2 consists of three different metallic and two different non-metallic elements.

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Zeitschrift Für Anorganische Und Allgemeine Chemie,
2012, 638 (10), 1482-1485.

Bi-phasic nanostructures for functional applications

Veith, Michael | Lee, Juseok | Martinez Miró, Marina | Akkan, Cagri Kaan | Dufloux, Cecile | Aktas, Oral C.

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Biphasic solid state composites of the type metal/metal oxide or element/element oxide can be synthesized in one pot chemical reactions using so called molecular "single source precursors". Due to their singular genesis these composites show peculiar hetero-structures based on core-shell hierarchies such as superlattices and composite nanospheres or nanowires. They exhibit superior or new functional properties compared to their individual constituent compounds. In the current work, we review in particular the synthetical and mechanistical approach of bi-phasic (Al/Al2O3) nanostructures such as nanospheres, nanowires and nanoloops using a single source precursor. Other bi-phasic materials of the general formula M/MOx (for example M = Ge, Sn, Pb) are addressed for comparison. The impact of different synthetical conditions as well as of modification of surfaces by laser techniques and their technological relevance are presented briefly. Additionally, functional applications of the prepared surfaces are explained with some outstanding case studies. These case studies are primarily concerned with their use as biomaterials and their application in medicine as well as with their use as thin films for optics and functional surfaces.

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Chemical Society Reviews,
2012, 41 (15), 5117-5130.

Investigation of morphological and electrical characteristics of tin doped indium oxide layers produced by a quasi single source precursor system

Veith, Michael | Bubel, Carsten | Grobelsek, Ingrid

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Sol-gel coatings of tin doped indium oxide (ITO) were prepared via spin-coating, using a quasi single source precursor system that enhances homogeneous distribution of the dopant tin inside the oxide lattice. In addition, the implementation of metastable, bivalent tin into the gel layer enables the application of a one-step heat treatment under inert atmosphere, eliminating the need for the usually required critical post reduction treatment after crystallisation. The ITO layers produced were uniformly polycrystalline, with a homogeneous thickness of 60 nm. They showed increased electrical conductivity and optical performance in terms of transmission (vis) and IR reflection. The texture was less pronounced and the tensile residual stress determined in the layers was lower than in similar films, manufactured in a conventional two-step annealing process.

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Thin Solid Films,
2012, 524, 67-74.