subject:(info eu repo classification ddc 570)

ETH Zürich

1. Berk, Christian. Alternative scaffolds for systemic delivery of small interfering RNAs.

Degree: 2019, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/415724

► Small interfering RNAs (siRNAs) are a promising class of RNA directed therapeutics. While exerting their gene-silencing activity similar to microRNAs (miRNAs) by recruiting the RNA… (more)

▼ Small interfering RNAs (siRNAs) are a promising class of RNA directed therapeutics. While exerting their gene-silencing activity similar to microRNAs (miRNAs) by recruiting the RNA induced silencing complex (RISC) toward messenger RNA (mRNA) targets, siRNAs are capable of inducing Argonaute-2 (AGO2) mediated target RNA cleavage. Despite the recent approval of patisiran, the first siRNA drug, systemic delivery remains a challenge and is currently limited to the liver. Whereas patisiran is dependent on lipid nanoparticle formulation (LNP), potent gene silencing has been achieved through naked administration of N-acetylgalactosamine (GalNAc) conjugated siRNAs. However, LNP-independent delivery requires the use of fully chemically modified siRNAs, which have raised concerns with respect to the formation of potentially toxic metabolites. Therefore, the goal of this work was to investigate alternative siRNA scaffolds which do not require a complex mixture of non-natural building blocks for systemic delivery. In the first approach, we investigated the use of fully phosphorothioate (PS) modified siRNAs. Full PS modification is commonly used in the design of single stranded antisense oligonucleotides (ASOs) and was shown to increase their binding to serum proteins. However, application of PS modifications to siRNA therapeutics has been restricted to the terminal positions due to conflicting reports on the activity and toxicity of full PS siRNAs. Our group recently reported the development of stereochemically biased PS siRNAs and demonstrated a higher activity of Rp- than Sp-enriched PS siRNAs in mammalian cells. Building on these results, we scaled up our synthesis protocol for PS siRNAs in order to characterize the biodistribution profile and the in vivo activity of a PS siRNA directed against the oncogene Lin28B. In addition, we investigated the albumin-binding capability and metabolic stability of various siRNA formats in biological fluids. In a second project, we adopted the previously described convertible nucleoside approach to introduce various chemical modifications into the major groove of siRNAs. We then evaluated polyamine conjugation as a means to increase the cellular uptake and nuclease stability of siRNAs under cell culture conditions. In a third project, we focused on the development of a new methodology to uncover the targetome of individual miRNAs. For this purpose, we synthesized 2’, 3’-cyclic phosphate terminated miRNA mimics (miRNA>p) which can be ligated to their RNA targets through the action of both an endogenous and an exogenously added RNA>p ligase. In addition, we contributed to several projects in the field of CRISPR-Cas genome editing and the development of a method to characterize surface-bound RNAs in a microarray-like setup. Advisors/Committee Members: Hall, Jonathan, Altmann, Karl-Heinz.

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA (6^th Edition):

Berk, C. (2019). Alternative scaffolds for systemic delivery of small interfering RNAs. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/415724

Chicago Manual of Style (16^th Edition):

Berk, Christian. “Alternative scaffolds for systemic delivery of small interfering RNAs.” 2019. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/415724.

MLA Handbook (7^th Edition):

Berk, Christian. “Alternative scaffolds for systemic delivery of small interfering RNAs.” 2019. Web. 27 Feb 2021.

Vancouver:

Berk C. Alternative scaffolds for systemic delivery of small interfering RNAs. [Internet] [Doctoral dissertation]. ETH Zürich; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/415724.

Council of Science Editors:

Berk C. Alternative scaffolds for systemic delivery of small interfering RNAs. [Doctoral Dissertation]. ETH Zürich; 2019. Available from: http://hdl.handle.net/20.500.11850/415724

ETH Zürich

2. Sabater Rullan, Marc. Optogenetic control of living cells and its applications.

Degree: 2019, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/416461

► Fueled by technological advances in DNA sequencing, laboratory automation, and a growing repository of parts, synthetic biology is yielding dividends; the engineering of biological circuits… (more)

▼ Fueled by technological advances in DNA sequencing, laboratory automation, and a growing repository of parts, synthetic biology is yielding dividends; the engineering of biological circuits is leading to successes in a broad range of areas, such as the bioproduction of novel compounds, or the therapeutic treatment of disease. However, a weak spot of most designs is their lack of robustness to environmental fluctuations or changes occurring in the host organism. One approach to tackle this issue is through feedback regulation; maintaining key nodes in the circuits constant by regularly measuring their abundance, comparing it with the desired value, and applying a corrective action. Circuits for feedback regulation can be encoded inside the cell itself in vivo control), or implemented externally (in silico control) by means of a computer able to influence cellular behavior. In this thesis, it is the latter that is on the spotlight; light-responsive cells were interfaced with platforms able to measure cellular behavior in real-time, and provide light inputs in order to achieve desired behaviors. In this manner, the strengths of in silico feedback control were capitalized to reduce variability in experimental outcome, precisely tune cellular processes and study the cells being regulated. The first work presented in the thesis is the construction of an automated platform for optogenetic regulation of bacterial populations. Using this experimental platform, we precisely regulated gene expression in Escherichia coli and showed how disturbances to the cells such as changes in media or temperature could be corrected by feedback control. In contrast, when no feedback mechanism was employed large differences in outcome were observed. Furthermore, using feedback we could control cellular growth, a process tightly regulated by the cell itself. In a second step, we built an experimental platform for single-cell optogenetic feedback control of Saccharomyces cerevisiae. Stochastic transcription was observed in real-time, and probing individual cells with optogenetic inputs revealed insights about this fundamental biological phenomenon. In addition, the large cell-to-cell variability inherent to the process could effectively be reduced by tuning the inputs sent to each cell. Finally, in the last work present in the thesis, the platform for single-cell feedback regulation was repurposed for the testing and characterization of biomolecular (in vivo) controllers. Biomolecular control motifs from the literature were implemented as stochastic chemical reaction networks in a computer. The biomolecular controllers were then interfaced with living cells by means of single-cell measurements and actuation. From these experiments, we could derive insights into conditions for adequate biomolecular performance, and pitfalls to avoid during their biological implementation. Advisors/Committee Members: Khammash, Mustafa Hani, id_orcid0000-0002-4855-9220, Zeilinger, Melanie, Panke, Sven, id_orcid0000-0002-9368-539X, Milias-Argeitis, Andreas.

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sabater Rullan, M. (2019). Optogenetic control of living cells and its applications. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/416461

Chicago Manual of Style (16^th Edition):

Sabater Rullan, Marc. “Optogenetic control of living cells and its applications.” 2019. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/416461.

MLA Handbook (7^th Edition):

Sabater Rullan, Marc. “Optogenetic control of living cells and its applications.” 2019. Web. 27 Feb 2021.

Vancouver:

Sabater Rullan M. Optogenetic control of living cells and its applications. [Internet] [Doctoral dissertation]. ETH Zürich; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/416461.

Council of Science Editors:

Sabater Rullan M. Optogenetic control of living cells and its applications. [Doctoral Dissertation]. ETH Zürich; 2019. Available from: http://hdl.handle.net/20.500.11850/416461

3. Mohr, Manuel A. Tools and Techniques for Single Cell Applications in Development and Neurobiology.

Degree: 2018, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/301753

► Fluorescence microscopy of genetically encoded fluorescent proteins (FPs) and biosensors has transformed modern biological research - a phenomenon often referred to as the "fluorescent protein… (more)

▼ Fluorescence microscopy of genetically encoded fluorescent proteins (FPs) and biosensors has transformed modern biological research - a phenomenon often referred to as the "fluorescent protein revolution". From the very beginning of this revolution, the discovery and engineering of new protein probes and the development of new microscopy modalities have mutually enabled each other. Prominently, breaking the fundamental diffraction limit of light in various super-resolution modalities was enabled by the discovery and engineering of photomodulatable FPs such as the photoactivatable paGFP or the photoconvertible FPs Dendra2 or EosFP. While photoconvertible FPs (pcFPs) are formidable markers for super-resolution microscopy and highlighting of structures or cells for pulse-chase-type experiments, they suffer from some key drawbacks for applications in complex, sensitive biological tissues. The near-ultraviolet (UV) light needed for efficient photoconversion cannot be axially confined inside tissue volumes, has limited tissue penetration and is phototoxic to light sensitive samples such as developing embryos. Primed conversion elegantly overcomes this requirement for near-UV light and can be axially confined to single cells in three dimensional tissues. However, this process has been limited to a single FP and remained mechanistically elusive, preventing protein engineering of probes as well as many biological applications. Following the introduction, in the second part of this thesis I describe my efforts to advance both the infrastructure and protein probes for primed conversion. I provide a detailed protocol for the simple, safe, and reproducible implementation of primed conversion into a commercial confocal laser scanning microscope (CLSM). Further, I uncover the mechanistic details underlying primed conversion and use this knowledge to engineer a host of pcFPs with improved characteristics for various primed conversion applications. I establish the first ever multi-color photoactvation localization microscopy (PALM)- scheme using two spectrally identical variants of mEos2, separating them solely based on their mode of photoconversion. Further, I provide a semiautomatic platform to use primed conversion of single blastomeres in a developing mouse embryo to computationally reorient the embryo and correct for the rapid movement and rotation, that would otherwise lead to the exclusion of the respective embryo from analysis. In the third part of this thesis I talk about a new class of genetically encoded Calcium ion (Ca2+) indicators GECIs, that we developed for two-photon (2P) imaging using cheap and powerful alternatives to the commonly used Titanium Sapphire (Ti::Sapph) lasers. We optimize several variants of the best in class GECIs of the GCaMP-series to excite efficiently at the center wavelength of non-tunable 1030nm Ytterbium-doped optical fiber lasers (YbFLs). This spectral shift allows for traditional 2P imaging using lasers of drastically reduced costs as well as kHz frame-rate imaging of Ca2+-dynamics using… Advisors/Committee Members: Pantazis, Periklis, Schreiter, Eric R., Platt, Randall J..

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mohr, M. A. (2018). Tools and Techniques for Single Cell Applications in Development and Neurobiology. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/301753

Chicago Manual of Style (16^th Edition):

Mohr, Manuel A. “Tools and Techniques for Single Cell Applications in Development and Neurobiology.” 2018. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/301753.

MLA Handbook (7^th Edition):

Mohr, Manuel A. “Tools and Techniques for Single Cell Applications in Development and Neurobiology.” 2018. Web. 27 Feb 2021.

Vancouver:

Mohr MA. Tools and Techniques for Single Cell Applications in Development and Neurobiology. [Internet] [Doctoral dissertation]. ETH Zürich; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/301753.

Council of Science Editors:

Mohr MA. Tools and Techniques for Single Cell Applications in Development and Neurobiology. [Doctoral Dissertation]. ETH Zürich; 2018. Available from: http://hdl.handle.net/20.500.11850/301753

ETH Zürich

4. Fouché, Simone. Drivers of genome evolution in a fungal pathogen of wheat.

Degree: 2020, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/425971

► Chromosome rearrangements involve duplication, deletions, inversions and translocations. Breakpoints of chromosome rearrangements are frequently in close proximity to transposable elements (TEs). TEs are known to… (more)

▼ Chromosome rearrangements involve duplication, deletions, inversions and translocations. Breakpoints of chromosome rearrangements are frequently in close proximity to transposable elements (TEs). TEs are known to mediate chromosome rearrangements through their own activity or through ectopic recombination. During this PhD we aimed to better understand the causes and consequences of chromosome rearrangements in Zymoseptoria tritici, an important pathogen of wheat. To study the origins of chromosome rearrangements the first chapter focusses on the de-repression of TEs, which is stress induced during a wheat infection cycle as well as in nutrient limited media. Stress was shown to drive epigenetic changes and trigger TE de-repression in multiple organisms. We find that TEs respond differently to stresses. Furthermore, effector genes in close proximity to TEs show a de-repression during early infection suggesting that TEs and effectors may be under the same epigenetic control. De-repressed TEs can place a mutational burden on the genome. Therefore, in the second chapter we aimed to quantify the number of chromosome rearrangements occurring in all 21 chromosomes in hundreds of progeny through a single round of meiosis. We find that the fidelity with which chromosomes go through meiosis differs between chromosomes. Chromosomes with a higher repeat content and lower synteny were less stable. In the final chapter we focused on a single rearranged chromosome that was generated by a self-fusion. We hypothesized that such a fused chromosome would go through degenerative breakage-fusion-bridge (BFB) cycles. Here we show the exact process whereby the highly unstable fused chromosome was created through ectopic recombination between a specific repeat family. We trace the fate of the novel chromosome through five rounds of meiosis and show that degenerative cycles occur through repeated ectopic recombination and non-disjunction. The ability of Z. tritici to tolerate chromosome duplications, losses and rearrangements makes this species a great model to observe and investigate the interplay between TE dynamics and chromosome rearrangements. Advisors/Committee Members: McDonald, Bruce A, Croll, Daniel, Suh, Alexander.

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fouché, S. (2020). Drivers of genome evolution in a fungal pathogen of wheat. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/425971

Chicago Manual of Style (16^th Edition):

Fouché, Simone. “Drivers of genome evolution in a fungal pathogen of wheat.” 2020. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/425971.

MLA Handbook (7^th Edition):

Fouché, Simone. “Drivers of genome evolution in a fungal pathogen of wheat.” 2020. Web. 27 Feb 2021.

Vancouver:

Fouché S. Drivers of genome evolution in a fungal pathogen of wheat. [Internet] [Doctoral dissertation]. ETH Zürich; 2020. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/425971.

Council of Science Editors:

Fouché S. Drivers of genome evolution in a fungal pathogen of wheat. [Doctoral Dissertation]. ETH Zürich; 2020. Available from: http://hdl.handle.net/20.500.11850/425971

ETH Zürich

5. Jordi, Christian Alain. Development of Proximity Ligation Assay variants for single cell proteomics.

Degree: 2020, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/426950

► Single cell analysis is a booming research field in biology. Cells are the fundamental building blocks of biological systems, and are therefore key to their… (more)

▼ Single cell analysis is a booming research field in biology. Cells are the fundamental building blocks of biological systems, and are therefore key to their understanding. For example it is necessary to study how they communicate with each other; how they organize themselves into larger structures like tissues, or the immune system. Understanding these processes has interesting implications for the study of diseases like cancer or chronic inflammation that can start from the dysregulation of single cells. Due to their small size, single cells cannot be studied using traditional biological methods that rely on the analysis of whole cell populations. Therefore new technologies are necessary. Some of the most promising advances have been made in the field of single cell mRNA sequencing. Through the application of microfluidic devices, it is now possible to sequence the mRNA of thousands of single cells. In comparison to that, the tools to analyse single cell protein content are still comparably limited. Since proteins catalyse most biological reactions, it would be more desirable to study biological systems on the protein level. In this thesis we took advantage of a protein analysis technique called the Proximity Ligation Assay (PLA) to develop new tools for single cell protein analysis. PLA relies on antibodies conjugated to short DNA strands. If two antibodies bind their target protein simultaneously, the short DNA molecules can be joined during a ligation step. This procedure allows to convert the presence of a protein into a DNA signal, and makes it possible to take advantage of highly developed DNA analysis methods like quantitative PCR, and Next Generation Sequencing (NGS). We developed a highly sensitive digital PLA assay that was able to reproducibly measure the protein content of single mammalian cells. This assay was combined with state of the art RT-PCR workflows to measure proteins, and mRNA from the same cell simultaneously. This revealed a very low correlation between mRNA, and protein expression levels in single cells, which stands in contrast to observations on the population level. PLA also has another interesting property. Due to the double recognition of target molecules it is possible to detect whether two proteins are in spatial proximity to each other. Since most proteins perform their function in complexes, this is a potentially very rich source of information. Therefore, we developed a PLA protocol that uses NGS to read out protein signals (PLA-Seq); like this, we were able to simultaneously measure 11 proteins, and their interactions. The new assay was tested using bulk samples, and was able to clearly distinguish two cell lines from each other based on their PLA signals. Since we designed PLA-Seq to be compatible with state of the art, high-throughput single cell RNA-Seq workflows we expect that it will soon be feasible to integrate our PLA-Seq assay in similar fashion, to allow high-throughput measurements of protein expression levels and their interactions. Advisors/Committee Members: Reddy, Sai, Tay, Savas, Treutlein, Barbara.

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jordi, C. A. (2020). Development of Proximity Ligation Assay variants for single cell proteomics. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/426950

Chicago Manual of Style (16^th Edition):

Jordi, Christian Alain. “Development of Proximity Ligation Assay variants for single cell proteomics.” 2020. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/426950.

MLA Handbook (7^th Edition):

Jordi, Christian Alain. “Development of Proximity Ligation Assay variants for single cell proteomics.” 2020. Web. 27 Feb 2021.

Vancouver:

Jordi CA. Development of Proximity Ligation Assay variants for single cell proteomics. [Internet] [Doctoral dissertation]. ETH Zürich; 2020. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/426950.

Council of Science Editors:

Jordi CA. Development of Proximity Ligation Assay variants for single cell proteomics. [Doctoral Dissertation]. ETH Zürich; 2020. Available from: http://hdl.handle.net/20.500.11850/426950

6. Seidel, Christoph-Maximilian. Steam Explosion Pretreatment of Lignocellulosic Biomass for Advanced Biofuels.

Degree: 2019, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/353549

► Biofuels as a sustainable replacement for fuels derived from fossil resources have gathered increasing interest in the past years due to environmental concerns about fossil… (more)

▼ Biofuels as a sustainable replacement for fuels derived from fossil resources have gathered increasing interest in the past years due to environmental concerns about fossil fuels and unstable oil supply. Lignocellulosic biomass like wood, energy crops or agricultural waste is the most abundant biological material on Earth and is considered as a potential source for sustainable biofuels. Intensive research is carried out on the biochemical conversion process, which consists of the enzyme-catalyzed hydrolysis of cellulose and hemicellulose into sugars and the fermentation of these sugars into the target product. Residual lignin is usually separated and burned for steam and power production but has also a great potential for the production of aromatic monomers. The complex entanglement of cellulose, hemicellulose and lignin makes a pretreatment necessary in order to obtain high yields of fermentable sugars in the subsequent enzymatic hydrolysis. Steam explosion will become most likely the dominating pretreatment technology due to its feedstock flexibility, its cost-savings potential and its comparatively low impact on the further bioprocessing. However, for very recalcitrant biomass, like softwood, steam explosion is not very effective and even after a pretreatment under severe conditions insufficient sugar yields are obtained in the subsequent hydrolysis. Preventing lignin repolymerization by adding a carbocation scavenger like 2-naphthol can significantly increase the enzymatic cellulose conversion in the subsequent hydrolysis. However, this process is still in its infancy and far from its industrial application. The effect of the explosive decompression and the presence of 2-naphthol during the pretreatment on different biomass feedstocks were investigated in order to gain further insight into the process and its application potential. The explosive decompression could significantly enhance the enzymatic cellulose digestibility of woody biomass by particle size reduction. Due to a less pronounced effect of particle size reduction in the pretreatment of herbaceous biomass (corn stover), only minor influences on the enzymatic hydrolysis could be observed. Hardwood (beech) and herbaceous biomass (corn stover) could not benefit from the presence of 2-naphthol during pretreatment as opposed to softwood (spruce). After a steam-pretreatment of beech wood with 2-naphthol even negative influences on the enzymatic digestibility could be observed. The investigation of substituted 2-naphthol molecules in the biomass structure by infraredspectroscopy suggests that 2-naphthol is not integrated into the lignin structure of hardwood. Nevertheless, fundamental investigations on lignin scavenger interactions remain necessary to find out why 2-naphthol only works with softwood. To obtain a homogeneous distribution of the almost non-water soluble 2-naphthol on the biomass, a dip-impregnation of the biomass is necessary. The requirement of large amounts of organic solvents has tremendous… Advisors/Committee Members: Rudolf von Rohr, Philipp, Panke, Sven, Studer, Michael.

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Seidel, C. (2019). Steam Explosion Pretreatment of Lignocellulosic Biomass for Advanced Biofuels. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/353549

Chicago Manual of Style (16^th Edition):

Seidel, Christoph-Maximilian. “Steam Explosion Pretreatment of Lignocellulosic Biomass for Advanced Biofuels.” 2019. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/353549.

MLA Handbook (7^th Edition):

Seidel, Christoph-Maximilian. “Steam Explosion Pretreatment of Lignocellulosic Biomass for Advanced Biofuels.” 2019. Web. 27 Feb 2021.

Vancouver:

Seidel C. Steam Explosion Pretreatment of Lignocellulosic Biomass for Advanced Biofuels. [Internet] [Doctoral dissertation]. ETH Zürich; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/353549.

Council of Science Editors:

Seidel C. Steam Explosion Pretreatment of Lignocellulosic Biomass for Advanced Biofuels. [Doctoral Dissertation]. ETH Zürich; 2019. Available from: http://hdl.handle.net/20.500.11850/353549

ETH Zürich

7. Sebastian, Bernhard. Shear force transmission across liposome membranes investigated by 3D flow tracing.

Degree: 2018, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/258461

► Cells in flowing environments are constantly exposed to mechanical stimuli from which they infer information about their environment and induce targeted responses. Sensing and conversion… (more)

▼ Cells in flowing environments are constantly exposed to mechanical stimuli from which they infer information about their environment and induce targeted responses. Sensing and conversion of mechanical stimuli into biochemical signalling is preceded by the propagation of these stimuli into the cell (mechanotransmission). Giant unilamellar vesicles (GUVs) are cell-sized liposomes which mimic the mechanical properties of the lipid plasma membrane. Due to their bottom-up construction from few, well-characterized constituents, GUVs are ideally suited for the quantitative study of mechanotranmission. This dissertation focuses on the investigation of mechanotransmission across GUV membranes. The great challenge for such studies lies in the visualization of GUV membrane and luminal flows in a time-resolved manner. The GUV membrane is a closed 3D surface which produces complex dynamics in response to shear, yet common visualization techniques are two-dimensional. Thus, the time-resolved measurement of these 3D dynamics across the entire GUV is a prerequisite for a comprehensive investigation of mechanotransmission. Therefore, the first milestone of this work was the development of a flow tracing method enabling 3D, time resolved measurements of membrane and luminal dynamics. Defocusing microscopy of fluorescent tracer particles enables determination of their positions in 3D. While confocal microscopes dispose all out-of-focus light, defocusing microscopy takes advantage of the phase information stored therein, enabling the extraction of 3D information from microscopy images. With this approach, the mechanotransmission of shear forces across GUV membranes was investigated. In this study, immobilized GUVs containing fluorescent tracer particles were exposed to variable shear flows. The results provide the first time-resolved visualization of 3D luminal flows and identify the principle parameters affecting mechanotransmission: local flow fields around the vesicle, external flow speed, and membrane composition. It was found that the shear field around the vesicle defines the luminal flow field inside GUVs. This effect is of geometric origin and not affected by the speed of the external flow and provides mechanical cues for cell orientation in shear flows. The impact of membrane composition on mechanotransmission was studied by addition of cholesterol, known to increase membrane viscosity. Mechanotransmission efficiency is the luminal flow speed in response to external shear flow speed at the vesicle apex, and was determined for different membrane compositions. An increase in cholesterol concentration, corresponding to minuscule increases membrane viscosity, was reliably measured in GUV membranes. These results demonstrate the sensitivity of the developed method and provide a tool for the detection of membrane composition in liposomal membranes, for which no other methods currently exist. In a second study, the effect of mechanotransmission on membrane dynamics was investigated. Fluorescent tracer particles were bound to lipids… Advisors/Committee Members: Schneider, Gisbert, Dittrich, Petra S..

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sebastian, B. (2018). Shear force transmission across liposome membranes investigated by 3D flow tracing. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/258461

Chicago Manual of Style (16^th Edition):

Sebastian, Bernhard. “Shear force transmission across liposome membranes investigated by 3D flow tracing.” 2018. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/258461.

MLA Handbook (7^th Edition):

Sebastian, Bernhard. “Shear force transmission across liposome membranes investigated by 3D flow tracing.” 2018. Web. 27 Feb 2021.

Vancouver:

Sebastian B. Shear force transmission across liposome membranes investigated by 3D flow tracing. [Internet] [Doctoral dissertation]. ETH Zürich; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/258461.

Council of Science Editors:

Sebastian B. Shear force transmission across liposome membranes investigated by 3D flow tracing. [Doctoral Dissertation]. ETH Zürich; 2018. Available from: http://hdl.handle.net/20.500.11850/258461

ETH Zürich

8. Fisser, Muriel Clea. The Role of MicroRNA-103/ 107 in Adipose Tissue and Natriuretic Peptide Receptor C- Mediated Targeting of White Adipocytes.

Degree: 2018, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/314942

► Over the past decades acquired type-2 diabetes mellitus has developed to be the prevalent metabolic disorder. Type-2 diabetes mellitus is characterized by chronic hyperglycemia and… (more)

▼ Over the past decades acquired type-2 diabetes mellitus has developed to be the prevalent metabolic disorder. Type-2 diabetes mellitus is characterized by chronic hyperglycemia and reduced insulin sensitivity in the liver, muscle and adipose tissues. This increased insulin resistance leads to hepatic steatosis, dysfunctional and inflamed adipose tissue, dyslipidemia and eventually to pancreatic β- cell failure. While white adipose tissue is associated with energy storage in the form of triglycerides, brown adipose tissue utilizes fatty acids to generate heat via Uncoupling Protein 1 (UCP1). Active brown adipose tissue is associated with a lower degree of obesity and white adipose tissue can undergo browning, i.e. take on brown adipose tissue characteristics, under certain conditions; the strongest known stimulus is a drop in body temperature. MicroRNAs, short noncoding RNAs can, via binding to specific mRNA targets induce their degradation and hence alter the transcriptome and metabolism of the cell. Knockdown of microRNA- 103/ 107 (mir-103/ 107) with antagomirs, microRNA antisense nucleotide oligos coupled to cholesterol, has proven to increase insulin sensitivity by increasing the mir-103/ 107 target Cav-1 in the liver of obese mice. However, the microRNAs were also suspected to influence adipose tissue metabolism in a Cav-1 independent mechanism. This could be caused by an increase of adipocyte number due to enhanced adipocyte progenitor differentiation, by browning of white adipocytes or by improved brown adipose tissue function. Unraveling the exact mechanisms and identification of the target tissues of mir-103/ 107 knockdown will help to understand the microRNAs’ function and to utilize it in the therapy of diabetes mellitus and obesity. Here we show that highest mir-103/ 107 expression levels are indeed found in the visceral adipose tissue of diabetic obese mice and furthermore that also the whitened brown adipose tissue of these mice expresses mir-103/ 107 at higher levels. In vivo knockdown of mir-103/ 107, coupled with a cold stimulus or denervation of the brown adipose tissue, resulted in enhanced insulin sensitivity, but the phenotype could not be determined to be caused by an improvement of adipose tissue function or browning of white adipose tissue. Mir-103/ 107 is endogenously expressed during adipogenesis of primary adipocyte progenitors and gain-of-function as well as loss-of-function of mir-103/ 107 during adipogenesis resulted in blocking of differentiation ex vivo. Knockdown of mir-103/ 107 in ex vivo differentiated primary adipocytes resulted in upregulation of the mRNA levels of Ucp1 and other brown adipose tissue markers. However, targets identified in a screen of the transcriptome after mir-103/ 107 knockdown were found to be regulated on the mRNA level but not on the protein level. Furthermore functional studies of ex vivo differentiated primary adipocytes revealed neither increased glucose and fatty acid uptake nor enhanced mitochondrial respiration after knockdown of mir-103/ 107.… Advisors/Committee Members: Stoffel, Markus, Kopf, Manfred, Wolfrum, Christian.

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA (6^th Edition):

Fisser, M. C. (2018). The Role of MicroRNA-103/ 107 in Adipose Tissue and Natriuretic Peptide Receptor C- Mediated Targeting of White Adipocytes. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/314942

Chicago Manual of Style (16^th Edition):

Fisser, Muriel Clea. “The Role of MicroRNA-103/ 107 in Adipose Tissue and Natriuretic Peptide Receptor C- Mediated Targeting of White Adipocytes.” 2018. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/314942.

MLA Handbook (7^th Edition):

Fisser, Muriel Clea. “The Role of MicroRNA-103/ 107 in Adipose Tissue and Natriuretic Peptide Receptor C- Mediated Targeting of White Adipocytes.” 2018. Web. 27 Feb 2021.

Vancouver:

Fisser MC. The Role of MicroRNA-103/ 107 in Adipose Tissue and Natriuretic Peptide Receptor C- Mediated Targeting of White Adipocytes. [Internet] [Doctoral dissertation]. ETH Zürich; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/314942.

Council of Science Editors:

Fisser MC. The Role of MicroRNA-103/ 107 in Adipose Tissue and Natriuretic Peptide Receptor C- Mediated Targeting of White Adipocytes. [Doctoral Dissertation]. ETH Zürich; 2018. Available from: http://hdl.handle.net/20.500.11850/314942

ETH Zürich

9. Böni, Lukas J. Biophysics and Biomimetics of Hagfish Slime.

Degree: 2018, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/329966

► Hagfish defend themselves with vast amounts of slime when provoked or attacked. The slime forms when so-called exudate, which consists of coiled up threads (‘skeins’)… (more)

▼ Hagfish defend themselves with vast amounts of slime when provoked or attacked. The slime forms when so-called exudate, which consists of coiled up threads (‘skeins’) and mucin vesicles is released into the surrounding seawater. Skeins resemble a ‘ball of wool’ as they are made of a single coiled up intermediate filament (IF) protein thread that is up to 30 cm long and 1 3 μm in diameter. Skeins unravel and create an underwater fiber network. Simultaneously, the mucin vesicles swell and burst and release mucin-like glycoproteins, which interact with the threads and together form hagfish slime. The secreted slime is a unique biomaterial as it is the most dilute and fastest forming hydrogel known to date. Furthermore, the fibers provide high elasticity and cohesiveness to the otherwise soft gel and were found to have similar properties to spider’s silk. Intrigued by its fast, efficient, and cold gelation, hagfish slime was used as a model to characterize and mimic high-performance marine soft materials. By pursuing a holistic ‘from fish to fiber’ approach, we investigated how slime can be harvested, stabilized, regenerated, and eventually transformed into novel biomimetic materials. In a first part, harvesting and stabilization of hagfish exudate is investigated, whereby two stabilization methods immersion in MCT (medium chain triglycerides) oil and dispersion in a high osmolarity citrate/PIPES (CP) buffer were compared. Using water retention measurements to assess the functionality of hagfish slime, it was shown that for short storage times (< five hours) both stabilization methods produced slime networks equal to fresh exudate. Longer storage times caused the exudate samples to degrade, whereby MCT samples formed clumps after about seven days, probably due to osmotic and temperature driven rupture of mucin vesicles. CP buffer stabilized samples, in contrast showed a gradual loss of functionality due to reduced skein unraveling. Long buffer exposure times caused less skeins to unravel and therefore less water was retained. It is likely that a seawater soluble glue, which holds the threads together and mediates unraveling denatures during storage in the buffer and becomes insoluble and thus decreases slime functionality. Having stabilization guidelines at hand, we dealt with the dynamics of slime formation. Motivated by the fact that this fibrous polyelectrolyte hydrogel efficiently and rapidly forms in a high ionic strength environment, we demonstrate the crucial role of ionic strength and seawater cations especially Ca2+ for the formation dynamics and functionality of hagfish slime. We suggest that sufficient ionic strength controls the dynamics of skein unraveling and slime network formation. A low ionic strength caused a confined and narrow thread network in contrast to the widespread and expanded network formed in seawater. In MilliQ thread skeins swelled and unraveled uncontrolled from both sides, causing tangling of the threads and thus preventing a widespread network. The fast unraveling in ion-free… Advisors/Committee Members: Windhab, Erich J., Vlassopoulos, Dimitris, Rühs, Patrick A..

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA (6^th Edition):

Böni, L. J. (2018). Biophysics and Biomimetics of Hagfish Slime. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/329966

Chicago Manual of Style (16^th Edition):

Böni, Lukas J. “Biophysics and Biomimetics of Hagfish Slime.” 2018. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/329966.

MLA Handbook (7^th Edition):

Böni, Lukas J. “Biophysics and Biomimetics of Hagfish Slime.” 2018. Web. 27 Feb 2021.

Vancouver:

Böni LJ. Biophysics and Biomimetics of Hagfish Slime. [Internet] [Doctoral dissertation]. ETH Zürich; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/329966.

Council of Science Editors:

Böni LJ. Biophysics and Biomimetics of Hagfish Slime. [Doctoral Dissertation]. ETH Zürich; 2018. Available from: http://hdl.handle.net/20.500.11850/329966

ETH Zürich

10. Wang, Yuluan. Tailoring CLIP-Based Methods for Exploring the miRNA Targetome.

Degree: 2019, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/334375

► MicroRNAs (miRNAs) are post-transcriptional regulators of protein-coding and other RNAs. Their main (canonical) function is the suppression of target RNAs which are recognised as such… (more)

▼ MicroRNAs (miRNAs) are post-transcriptional regulators of protein-coding and other RNAs. Their main (canonical) function is the suppression of target RNAs which are recognised as such through its binding to an often conserved and partially complementary sequence. The miRNA is responsible for target recognition and guides the miRNA induced silencing complex (RISC) machinery to the targets, where posttranscriptional regulations are effected. Since targeting only requires partial complementarity in the interaction site, a single miRNA is able to regulate many transcripts. Given that miRNAs are involved in many important physiological- and disease-development processes, the RNA field has invested significantly in methods to increase the understanding of these small RNAs. Some targeting rules have been described and established. Most of the canonical targeting motives have been confirmed by many different groups, explaining a major part of miRNA functions and targeting rules. Nevertheless, more recent findings of less biased target identification methods have confirmed the importance of non-canonical targeting. In this thesis, we confirmed the applicability of a previously developed technique - miRNA crosslinking and immunoprecipitation (miR-CLIP). The protocol uses psoralen and biotin bis-modified pre-miRNAs and was shown to be useful for identification of canonical and non-canonical targets. In one of the projects, we used miR-CLIP to capture the targetome of miR-124 and miR-132, two brain-enriched 3p miRNAs. In course of these studies, we optimized the protocol and validated many of the captured miR-124 and miR-132 specific targets. In addition, we confirmed the suitability of the protocol for capturing targetomes of 3p miRNAs. We also compared the targetomes from two differently modified probes. Finally, our data revealed a biased processing of miR-124 in non-neuronal cells. Recent developments of chimera-generating methods have uncovered new insights into miRNA-target recognition. By physically ligating the miRNA to its target sites, non-canonical interaction-sites are captured as covalently attached sequences to the miRNA. We attempted to develop a new chimera-generating method - cyCLIP - based on a ligase, which joins 2'3-cyclic phosphate to the 5'-OH of a target RNA. We established the ligation of chemically-synthesized 2'3'-cyclic phosphate miRNAs and optimized several steps of the protocol. However, first attempts to sequence a cyCLIP library revealed very few chimeras bearing the full length miRNAs. This new method will be further investigated and pursued. Advisors/Committee Members: Hall, Jonathan, Ciaudo, Constance.

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wang, Y. (2019). Tailoring CLIP-Based Methods for Exploring the miRNA Targetome. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/334375

Chicago Manual of Style (16^th Edition):

Wang, Yuluan. “Tailoring CLIP-Based Methods for Exploring the miRNA Targetome.” 2019. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/334375.

MLA Handbook (7^th Edition):

Wang, Yuluan. “Tailoring CLIP-Based Methods for Exploring the miRNA Targetome.” 2019. Web. 27 Feb 2021.

Vancouver:

Wang Y. Tailoring CLIP-Based Methods for Exploring the miRNA Targetome. [Internet] [Doctoral dissertation]. ETH Zürich; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/334375.

Council of Science Editors:

Wang Y. Tailoring CLIP-Based Methods for Exploring the miRNA Targetome. [Doctoral Dissertation]. ETH Zürich; 2019. Available from: http://hdl.handle.net/20.500.11850/334375

11. Santos Teixeira, Frederico. Development and Application of a High Performance Computing Framework for the Realistic Mechanobiological Modeling of Patient-Specific Aneurysm Disease Evolution.

Degree: 2019, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/381777

► Intracranial or cerebral aneurysm is a ballooning of the vessel wall due to a pathological remodeling specific to intracranial vessels feeding the cerebrum. In 2-3%… (more)

▼ Intracranial or cerebral aneurysm is a ballooning of the vessel wall due to a pathological remodeling specific to intracranial vessels feeding the cerebrum. In 2-3% of the cases, the outpouching may rupture and allow blood to leak into the surrounding tissues, and potentially massively increase the intracranial pressure and reduce or interrupt brain perfusion. On average, 10% of aneurysm rupture patients die before receiving medical attention, 25% in the first 24 hours and another 25% within six months due to related complications. Not the least because of the high mortality rate connected to aneurysm rupture, a comprehensive understanding of this serious disease is urgently needed. Thanks to recent advancements in imaging technologies, cerebral aneurysms are being detected more regularly, often as a secondary diagnosis in clinical examinations. However, as a result, physicians are challenged, as they are forced to make decisions on the further course of treatment while taking into account various factors such as small rupture rates, treatment risks, high financial costs, and the psychological effects, e.g., anxiety, depression on the patients. Historically, aneurysm rupture risk is usually assessed through simple geometric scores, i.e., aneurysm size and location (aspect ratio and shape have been suggested by not yet validated in a good clinical setting). Yet, due to the availability of high-contrast imaging technologies that provide spatially resolved information about, e.g., the status of the vessel wall, the focus of rupture risk assessment is gradually shifting to the patient-specific characterization of the aneurysm wall and its exposure to the hemodynamic environment. Mechanobiological modeling (mathematical and computational) of mechanical wall-exposure and ensuing tissue remodeling can assist image-based evaluation of aneurysm stability and increase the mechanistic understanding of disease inception and evolution, and thus play an important role in both diagnosis and investigative. This thesis provides an integrated, comprehensive framework for aneurysm disease characterization and evolution modeling which covers all the steps from image-based creation of patient-specific aneurysm and vasculature models, to morphological shape-analyses, fluid dynamical exposure assessment, biomechanical wall modeling, and (sub)cellular wall constituents-based disease growth and remodeling simulation. The implementation of the disease evolution model - driving flow and wall-exposure metrics, biomechanical wall characteristics, and wall constituent evolution - can be easily adapted, by modifying corresponding formulas in a Python script, to provide researchers with a powerful tool to explore hypotheses on disease inception and evolution. The framework is unique, as the simulation of flow, growth, and remodeling of intracranial aneurysms is enabled, with realistic modeling of (i) flow boundary conditions; (ii) personalized vascular geometries; (iii) inhomogeneous processes in and properties of the vascular wall; (iv)… Advisors/Committee Members: Huang, Qiuting, Kuster, Niels, Kurtcuoglu, Vartan.

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA (6^th Edition):

Santos Teixeira, F. (2019). Development and Application of a High Performance Computing Framework for the Realistic Mechanobiological Modeling of Patient-Specific Aneurysm Disease Evolution. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/381777

Chicago Manual of Style (16^th Edition):

Santos Teixeira, Frederico. “Development and Application of a High Performance Computing Framework for the Realistic Mechanobiological Modeling of Patient-Specific Aneurysm Disease Evolution.” 2019. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/381777.

MLA Handbook (7^th Edition):

Santos Teixeira, Frederico. “Development and Application of a High Performance Computing Framework for the Realistic Mechanobiological Modeling of Patient-Specific Aneurysm Disease Evolution.” 2019. Web. 27 Feb 2021.

Vancouver:

Santos Teixeira F. Development and Application of a High Performance Computing Framework for the Realistic Mechanobiological Modeling of Patient-Specific Aneurysm Disease Evolution. [Internet] [Doctoral dissertation]. ETH Zürich; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/381777.

Council of Science Editors:

Santos Teixeira F. Development and Application of a High Performance Computing Framework for the Realistic Mechanobiological Modeling of Patient-Specific Aneurysm Disease Evolution. [Doctoral Dissertation]. ETH Zürich; 2019. Available from: http://hdl.handle.net/20.500.11850/381777

ETH Zürich

12. Graham, Jenna. Fibronectin as a key regulator of macromolecular crowding-enhanced extracellular matrix assembly.

Degree: 2019, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/400019

► Tissue engineers seek to replace damaged and diseased tissues in the body with in vitro-grown tissue substitutes. This involves seeding cells onto an engineered scaffold… (more)

▼ Tissue engineers seek to replace damaged and diseased tissues in the body with in vitro-grown tissue substitutes. This involves seeding cells onto an engineered scaffold and providing the right chemical and physical cues to promote cell-mediated tissue assembly and tissue-specific remodeling. One of the key factors limiting the success of tissue engineering is the long culture time required for cells to assemble matrix in the highly dilute cell culture medium. However, the in vivo environment where matrix assembly naturally occurs is not dilute like cell culture medium, but rather highly crowded by macromolecules. Studies have shown that adding soluble macromolecules to cell culture medium to mimic the natural macromolecular crowding enables cells to more effectively build matrix by promoting molecular interactions. Most mechanistic studies of how crowding enhances matrix assembly focus on the impact of crowding on collagen fiber assembly and largely ignore the highly abundant provisional matrix protein fibronectin. Fibronectin is the first matrix protein assembled by cells and it serves as a template to nucleate collagen fibers. Collagen cannot be assembled in the absence of fibronectin, and the tensional state of fibronectin impacts collagen binding. In this work we asked for the first time what role fibronectin plays in the underpinning mechanism of crowding-enhanced matrix assembly. First, we took a close look at fibronectin and collagen I assembly over time and showed that the assembly of both is increased by the neutral crowding molecule Ficoll and the two are colocalized in the early stages of matrix assembly. We then asked how crowding enhances fibronectin assembly, since this process is cell tension-mediated and does not rely on enzymatic cleavage like collagen assembly does. We found that there were no changes in cell mechanical behavior, including contractility, that could explain the increased assembly. We then tuned to the fibronectin and found that Ficoll doubles the amount of surface adherent fibronectin, which can be readily harvested by fibroblasts and speed up fibrillogenesis, thus providing evidence of the first mechanism for crowding enhanced fibronectin assembly. Next we asked what role fibronectin plays in the assembly of collagen in the presence of crowding. We used our well-validated Fn-FRET probe to reveal that Ficoll crowding upregulates the total amount of fibronectin fibers in a low-tension state through upregulating fibronectin assembly. Since unstretched fibronectin fibers have more collagen binding sites to nucleate the onset of collagen fibrillogenesis, our data suggests that the Ficoll-induced upregulation of low-tension fibronectin fibers contributes to enhanced collagen assembly in crowded conditions. We then manipulated the fibronectin assembly process by cross-linking fibronectin to the glass surface and found that fibroblasts could no longer harvest the coating to assemble early fibers. Remarkably, this suppressed the Ficoll-induced upregulation of collagen… Advisors/Committee Members: Vogel, Viola, Raghunath, Michael, Wirtz, Denis.

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA (6^th Edition):

Graham, J. (2019). Fibronectin as a key regulator of macromolecular crowding-enhanced extracellular matrix assembly. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/400019

Chicago Manual of Style (16^th Edition):

Graham, Jenna. “Fibronectin as a key regulator of macromolecular crowding-enhanced extracellular matrix assembly.” 2019. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/400019.

MLA Handbook (7^th Edition):

Graham, Jenna. “Fibronectin as a key regulator of macromolecular crowding-enhanced extracellular matrix assembly.” 2019. Web. 27 Feb 2021.

Vancouver:

Graham J. Fibronectin as a key regulator of macromolecular crowding-enhanced extracellular matrix assembly. [Internet] [Doctoral dissertation]. ETH Zürich; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/400019.

Council of Science Editors:

Graham J. Fibronectin as a key regulator of macromolecular crowding-enhanced extracellular matrix assembly. [Doctoral Dissertation]. ETH Zürich; 2019. Available from: http://hdl.handle.net/20.500.11850/400019

ETH Zürich

13. Arias-Sánchez, Flor I. Bacterial and viral adaptation in ecologically complex systems.

Degree: 2018, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/316339

► If we want to understand microbial diversity and find new ways to control infectious disease, it is important that we consider the variety of ecological… (more)

▼ If we want to understand microbial diversity and find new ways to control infectious disease, it is important that we consider the variety of ecological factors that microorganisms normally encounter and how this influences their evolution. Our understanding of interactions between abiotic (e.g. antibiotics) and biotic (e.g. parasites) conditions, and how they affect microbial adaptation remains limited. Specifically, the role of viruses that infect bacteria (phages) in the evolution of antibiotic resistance is an area of growing interest. Not only because viral parasites are important in bacterial ecology and evolution, but also because they have the potential to be used therapeutically. In this thesis I develop and test hypotheses relating to bacterial and viral adaptation in ecologically complex systems. In chapter 1 I give a general introduction to the thesis. In chapter 2, I investigated the role of antibiotic resistance alleles in bacterial responses to parasitic viruses (phages). I show that although some antibiotic resistance alleles can impede the evolution of resistance to phages via growth costs, the overall effect of resistance alleles is relatively weak, as compared to the strong effect of a mutator allele. In chapter 3 I investigated the counteracting effects of antibiotics on bacterial adaptation, specifically, the alteration of mutation supply rates via changes in bacterial population size or bacterial mutation rates. I present evidence that positive mutagenic effects are relatively weak, as compared to the strong negative effects of antibiotics in reducing population size. In chapter 4 I investigated phage host shifting across a range of different bacterial hosts. I used experimental evolution to evolve phage in the presence of novel bacterial host strains. I provide evidence that evolution can result in host shifts, but also in a variety of changes in virulence towards other hosts. In chapter 5 I outline some of the broad themes that emerge from these research projects and point out some of the potential areas for future work. Advisors/Committee Members: Hall, Alex, id_orcid0000-0002-3654-1373, Becks, Lutz, Velicer, Gregory J..

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA (6^th Edition):

Arias-Sánchez, F. I. (2018). Bacterial and viral adaptation in ecologically complex systems. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/316339

Chicago Manual of Style (16^th Edition):

Arias-Sánchez, Flor I. “Bacterial and viral adaptation in ecologically complex systems.” 2018. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/316339.

MLA Handbook (7^th Edition):

Arias-Sánchez, Flor I. “Bacterial and viral adaptation in ecologically complex systems.” 2018. Web. 27 Feb 2021.

Vancouver:

Arias-Sánchez FI. Bacterial and viral adaptation in ecologically complex systems. [Internet] [Doctoral dissertation]. ETH Zürich; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/316339.

Council of Science Editors:

Arias-Sánchez FI. Bacterial and viral adaptation in ecologically complex systems. [Doctoral Dissertation]. ETH Zürich; 2018. Available from: http://hdl.handle.net/20.500.11850/316339

ETH Zürich

14. Enke, Tim N. Life at the Micro-Scale - Marine Microbial Ecology on Model Particulate Organic Matter.

Degree: 2018, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/316558

► Microbes play a crucial role in global-scale ecosystem processes such as marine carbon cycling. Bridging the gap between the micro-scale at which ecological interactions between… (more)

▼ Microbes play a crucial role in global-scale ecosystem processes such as marine carbon cycling. Bridging the gap between the micro-scale at which ecological interactions between bacteria unfold and the orders-of-magnitude larger ecosystem-scale is one of the major challenges in microbial ecology. Here, we address this gap by investigating how communities of bacteria assemble on and degrade model particulate organic matter, a crucial process in biological carbon cycling in the marine environment. We aim to answer a central question in microbial ecology: how microbial communities reproducibly self-organize and if those dynamics can be predicted. We first track the taxon dynamics of bacteria attached to different types of model marine particles and demonstrate that particle-attached communities undergo reproducible successions. Moreover, we discover two ecological strategies of particle attached bacteria: in one, bacteria attach to all particle types alike and, in the other, they selectively colonize one particle type. The partitioning into ecological strategies reveals simple, modular design principles in community assembly dynamics during particulate organic matter decomposition. We next link micro-scale ecology –the interactions between microbes that coexist in close proximity– of model marine microbial communities to community function, in this case turnover of particulate organic matter. We find that interactions between two major functional classes of bacteria, primary particle degraders and secondary, non-degrading consumers, regulate particulate organic matter turnover. Secondary consumers decrease particle degradation rates as they compete for available resources such as carbon or physical space, thereby altering the dynamics of carbon cycling and remineralization in the ocean. The demonstrated regulation of particulate organic matter turnover by ecological interactions between two major groups of bacteria and the observed taxonomic shifts during the successional transitions that shape particle attached microbial communities contribute to our understanding of the effect of microbial ecology at the micro-scale on global-scale ecosystem processes. Advisors/Committee Members: Ackermann, Martin, Cordero, Otto X., Claassen, Manfred.

Subjects/Keywords: info:eu-repo/classification/ddc/570; Life sciences

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APA (6^th Edition):

Enke, T. N. (2018). Life at the Micro-Scale - Marine Microbial Ecology on Model Particulate Organic Matter. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/316558

Chicago Manual of Style (16^th Edition):

Enke, Tim N. “Life at the Micro-Scale - Marine Microbial Ecology on Model Particulate Organic Matter.” 2018. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/316558.

MLA Handbook (7^th Edition):

Enke, Tim N. “Life at the Micro-Scale - Marine Microbial Ecology on Model Particulate Organic Matter.” 2018. Web. 27 Feb 2021.

Vancouver:

Enke TN. Life at the Micro-Scale - Marine Microbial Ecology on Model Particulate Organic Matter. [Internet] [Doctoral dissertation]. ETH Zürich; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/316558.

Council of Science Editors:

Enke TN. Life at the Micro-Scale - Marine Microbial Ecology on Model Particulate Organic Matter. [Doctoral Dissertation]. ETH Zürich; 2018. Available from: http://hdl.handle.net/20.500.11850/316558

ETH Zürich

15. Huber, Rebecca P. Morphological Gradients for Protein-Adsorption and Blood-Coagulation Studies.

Degree: 2018, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/269701

► Gradient surfaces with a continuously changing surface parameter allow rapid, high-throughput investigations and systematic studies in tribology, adhesion and biology. Surface roughness is an important… (more)

▼ Gradient surfaces with a continuously changing surface parameter allow rapid, high-throughput investigations and systematic studies in tribology, adhesion and biology. Surface roughness is an important surface parameter on both micrometer and nanometer scales. In this thesis, different methods for the fabrication of micro- and/or nano-featured morphology gradients and their applications in biology are described. Nanoparticle-density gradients were produced by a simple dip-coating process of a positively charged poly(ethylene imine) (PEI)-coated silicon wafer into a negatively charged silica-nanoparticle suspension. To ensure firm anchoring of the particles to the surface the gradients were sintered at 1050 °C. All fabricated gradients were extensively characterized by SEM and AFM. Gradients were coated with TiO2 to mimic the surface of bone implants. A step-by-step in vivo like model that follows the natural processes occurring after implantation of an osseous implant was chosen to study the effect of nano-rough surfaces on protein adsorption, blood coagulation as well as cell behavior. TiO2-coated nanoparticle-density gradients were used for protein-adsorption studies. For gradients with 39- and 72-nm-diameter nanoparticles no influence of nano-features on the amount of adsorbed proteins could be found. In contrast, for gradients with 12-nm-diameter nanoparticles, fibrinogen in competition with albumin and fibronectin or serum, showed a higher adsorption at the high-particle-density end of the gradient. Blood-coagulation studies revealed that nanostructures involving 39-nm-diameter nanoparticles seem to enhance blood coagulation. With an increase in 39 nm particle-density, faster fibrin-network formation was observed, while smaller (12 nm) and bigger (72 nm) nanoparticles did not influence the activation of platelets or the fibrin-network formation. Monoclonal-antibody binding specific for the dodecapeptide sequence of the fibrinogen γ chain was measured on fibrinogen adsorbed onto nanoparticle-density gradients to gain further insight into the correlation between the protein and blood experiments. The ratio of antibody to adsorbed fibrinogen decreased by approximately 65% with increasing nanoparticle density for 39 nm particles, indicating conformational changes of adsorbed fibrinogen along the gradient. Human-bone-cell (HBC) experiments performed on nano-roughness gradients exhibited a gradual change in the cell behavior along the gradient with decreasing proliferation with decreasing inter-particle distance. Ten days post seeding, the number of HBCs on 39 nm particle-density gradients was six times higher at positions without particles compared to the high-density end of the gradient. Since biological experiments require a large number of substrates, different replication techniques were used to create copies of master gradients. Injection molding from polymer inserts was shown to be a successful replication technique for the mass production of samples with 72 nm features. For smaller… Advisors/Committee Members: Spencer, Nicholas, Maniura, Katharina, Berner, Simon, Vörös, Janos.

Subjects/Keywords: info:eu-repo/classification/ddc/610; info:eu-repo/classification/ddc/570; Medical sciences, medicine; Life sciences

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APA (6^th Edition):

Huber, R. P. (2018). Morphological Gradients for Protein-Adsorption and Blood-Coagulation Studies. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/269701

Chicago Manual of Style (16^th Edition):

Huber, Rebecca P. “Morphological Gradients for Protein-Adsorption and Blood-Coagulation Studies.” 2018. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/269701.

MLA Handbook (7^th Edition):

Huber, Rebecca P. “Morphological Gradients for Protein-Adsorption and Blood-Coagulation Studies.” 2018. Web. 27 Feb 2021.

Vancouver:

Huber RP. Morphological Gradients for Protein-Adsorption and Blood-Coagulation Studies. [Internet] [Doctoral dissertation]. ETH Zürich; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/269701.

Council of Science Editors:

Huber RP. Morphological Gradients for Protein-Adsorption and Blood-Coagulation Studies. [Doctoral Dissertation]. ETH Zürich; 2018. Available from: http://hdl.handle.net/20.500.11850/269701

ETH Zürich

16. Mayerhofer, Johanna. Stability of soil microbial communities to applications of the fungal biological control agent Metarhizium brunneum.

Degree: 2017, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/244602

► Naturally occurring entomopathogens, including fungi, bacteria, protozoa, nematodes and viruses, are important for natural regulation of insect populations and therefore used in biological control of… (more)

▼ Naturally occurring entomopathogens, including fungi, bacteria, protozoa, nematodes and viruses, are important for natural regulation of insect populations and therefore used in biological control of insect pests. Biological control using entomopathogens is an alternative pest management strategy to chemical control, is considered to be more environmental friendly than chemical control and is often part of integrated pest management (IPM). Beneficial effects of entomopathogens as compared to chemicals may include conservation of other natural enemies, reduction of pesticide residues in soil and plants as well as safety for non-target organisms. The development of existing biological control for important soil dwelling pests in Europe by exploiting novel application strategies and synergistic effects of entomopathogenic fungi, entomopathogenic nematodes and natural substances, has been the major aim of the EU-project supporting this thesis (INBIOSOIL). Biological control using entomopathogenic fungi may include soil applications of large quantities of fungal propagules, often resulting in densities of up to 1014 propagules per ha. Such mass applications and introductions of microorganisms to soil may affect indigenous soil microbial communities and the ecosystem functions they fulfil. Assessment of potential effects of applied microorganisms on native soil microbial communities is therefore important and also required in the registration process of novel products by European and Swiss regulations. Species of the entomopathogenic fungal genus Metarhizium are widely used in biological control and potential effects of Metarhizium on native soil microbial communities have barely been investigated. As a basic principal of risk assessment of mass applications it is mandatory to verify that soil microbial communities are exposed to the applied fungal biological control agent (BCA). It is important to be able to determine both exposure (presence and abundance) as well as effects, e.g., changes in microbial community structures, of a BCA in soil as basis of a risk assessment. Therefore, the aims of this thesis were I) to improve molecular tools to assess presence and abundance of the BCA in soil in order to track exposure of soil microbial communities and II) to assess potential effects of applications of two strains of the BCA on soil microbial communities in pot and field experiments and III) to investigate potential analytical constraints of the presence of one highly abundant microbial strain on the assessment of changes in soil microbial community structures. Exposure of soil microbial communities to the BCA was assessed by isolation of Metarhizium spp. from soil on selective medium and subsequently identifying the genotype of the applied strains using simple sequence repeat (SSR) marker analyses. To optimize the typing tool the transferability of 41 existing SSR markers to different Metarhizium spp. were investigated (Chapter 2). This was particularly important since structure and taxonomy within the genus Metarhizium… Advisors/Committee Members: Leuchtmann, Adrian, McDonald, Bruce A., Enkerli, Jürg, Vidal, Stefan.

Subjects/Keywords: info:eu-repo/classification/ddc/570; info:eu-repo/classification/ddc/630; Life sciences; Agriculture

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APA (6^th Edition):

Mayerhofer, J. (2017). Stability of soil microbial communities to applications of the fungal biological control agent Metarhizium brunneum. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/244602

Chicago Manual of Style (16^th Edition):

Mayerhofer, Johanna. “Stability of soil microbial communities to applications of the fungal biological control agent Metarhizium brunneum.” 2017. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/244602.

MLA Handbook (7^th Edition):

Mayerhofer, Johanna. “Stability of soil microbial communities to applications of the fungal biological control agent Metarhizium brunneum.” 2017. Web. 27 Feb 2021.

Vancouver:

Mayerhofer J. Stability of soil microbial communities to applications of the fungal biological control agent Metarhizium brunneum. [Internet] [Doctoral dissertation]. ETH Zürich; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/244602.

Council of Science Editors:

Mayerhofer J. Stability of soil microbial communities to applications of the fungal biological control agent Metarhizium brunneum. [Doctoral Dissertation]. ETH Zürich; 2017. Available from: http://hdl.handle.net/20.500.11850/244602

ETH Zürich

17. Stroheker, Sophie. Community dynamics and transmission within the Phialocephala fortinii s.l. - Acephala applanata species complex.

Degree: 2017, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/248430

► Just about all plants are colonized by fungal endophytes. Dark septate endophytes (DSE) are a diverse group of ascomycetes colonizing roots of a vast number… (more)

▼ Just about all plants are colonized by fungal endophytes. Dark septate endophytes (DSE) are a diverse group of ascomycetes colonizing roots of a vast number of plants in many different ecosystems. Considering the Northern hemisphere, the majority of DSE belong to the Phialocephala fortinii s.l. - Acephala applanata species complex (PAC), consisting of at least 21 morphologically indistinguishable cryptic species (CSP), to seven of which species rank was formally assigned. CSP are reproductively isolated and so far no teleomorphic form of the fungus has been found, even tough evidence exists that sexual reproduction occurs or has occurred in the past. PAC communities are highly diverse and still little is known about the factors influencing community formation. Even though PAC are highly successful root colonizers, their ecological function is poorly understood. Therefore, community structure and dynamics, competition and possible modes of transmission were investigated within the scope of this thesis. In a first study, spatial and temporal dynamics of a PAC community in an undisturbed Norway spruce (Picea abies) forest, originally assessed in 2004, were reassessed ten years later. The spectrum of species remained virtually the same over this period. In both years, a majority of isolates belonged to Phialocephala turicensis, Phialocephala letzii, Phialocephala europaea, and Phialocephala helvetica and a trend towards fewer species per sampling plot could be observed. Microsatellite analysis revealed that none of the PAC genotypes detected in 2004 were present at the same grid points in 2014. Furthermore, only four of the 22 genotypes detected in 2004 were found again in 2014, indicating recombination. Recognizing that the PAC community is subjected to both spatial and temporal changes, the competitiveness of three P. subalpina strains and two P. fortinii s.s. strains was tested under laboratory conditions in living roots of inoculated Norway spruce saplings. Saplings were first colonized by a “resident” strain (“primary colonizer”) followed by transplantation into a substrate colonized by the “invading” strain (“secondary colonizer”). Power of retention and power of colonization were calculated for each strain. Overall, the strains clearly differed in their ability to colonize roots, as well as in their capability of offering resistance against an invading strain, and also in their power of suppressing an already established “resident” strain within living roots. With the possibility of inoculating Norway spruce saplings, transmission of PAC was tested using three different set-ups in a semi-sterile substrate: (I) without root contact by separating inoculated and non-inoculated saplings with a fine mesh, (II) confrontation of a non-inoculated sapling wrapped in fine mesh with a colonized substrate without contact, and (III) direct root contact between inoculated and non- inoculated spruce. PAC was transmitted most successfully via direct root contact between saplings, followed by saplings confronted with the… Advisors/Committee Members: Holdenrieder, Ottmar, McDonald, Bruce A, Helander, Marjo, Sieber, Thomas N..

Subjects/Keywords: info:eu-repo/classification/ddc/570; info:eu-repo/classification/ddc/580; Life sciences; Botanical sciences

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APA (6^th Edition):

Stroheker, S. (2017). Community dynamics and transmission within the Phialocephala fortinii s.l. - Acephala applanata species complex. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/248430

Chicago Manual of Style (16^th Edition):

Stroheker, Sophie. “Community dynamics and transmission within the Phialocephala fortinii s.l. - Acephala applanata species complex.” 2017. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/248430.

MLA Handbook (7^th Edition):

Stroheker, Sophie. “Community dynamics and transmission within the Phialocephala fortinii s.l. - Acephala applanata species complex.” 2017. Web. 27 Feb 2021.

Vancouver:

Stroheker S. Community dynamics and transmission within the Phialocephala fortinii s.l. - Acephala applanata species complex. [Internet] [Doctoral dissertation]. ETH Zürich; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/248430.

Council of Science Editors:

Stroheker S. Community dynamics and transmission within the Phialocephala fortinii s.l. - Acephala applanata species complex. [Doctoral Dissertation]. ETH Zürich; 2017. Available from: http://hdl.handle.net/20.500.11850/248430

ETH Zürich

18. Carrera, Dániel Árpád. Defining key proteins of the primary carbohydrate metabolism in Arabidopsis thaliana.

Degree: 2017, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/258247

► Photosynthetic assimilation of atmospheric carbon dioxide (CO2) is the major carbon fixation mechanism. Thereby the captured light energy is used to produce carbohydrates within the… (more)

▼ Photosynthetic assimilation of atmospheric carbon dioxide (CO2) is the major carbon fixation mechanism. Thereby the captured light energy is used to produce carbohydrates within the Calvin-Benson cycle. A portion of the synthesized carbohydrates is exported out of the chloroplast into the cytosol, where sucrose can be produced. Sucrose is a non-reducing, neutral disaccharide, which can be transported throughout the plant, providing the necessary carbon and energy for development. The Calvin-Benson cycle and cytosolic sucrose metabolism build a complex network consisting of many highly regulated biochemical reactions. One characteristic of primary carbohydrate metabolism in plants is the apparent high level of genetic redundancy, especially among the cytosolic sucrose-metabolic enzymes. While the biochemical reactions are relatively well described, the role of the single isoforms is still unclear, and the apparent redundant isoforms might have a metabolic and physiological role. The aim of this work was to unravel and clarify the function of these (iso)enzymes and, if possible, attribute specific functions to them. First, homozygous single knock-out mutants were screened for phenotypic differences under normal growth conditions. This rarely revealed significant alterations compared to the wild type, suggesting that the isoenzymes may actually be redundant. However, as plants are naturally constantly exposed to environmental fluctuations, the roles of the isoforms may become apparent during acclimation. We therefore established a hydroponic platform, where plants could be grown in well-defined nutrient-deficient media (either without nitrate or phosphate) and under mild long-term abiotic stresses (cold, warm, salt or osmotic stress). This allowed me to perform a comparative proteomic analysis in wild type plants, where the plants’ stress responses to different treatments were examined in both the shoot and the root (Chapter 1). My results suggested that the plants response to the different stresses in a very specific manners. Furthermore, these responses were distinct in the root and the shoot. To link the changes in the proteome with changes at the metabolic level, we also measured carbohydrates in the hydroponically grown plants (Chapter 2). Moreover, I selected promising candidates based on the proteomic analyses, i.e. sucrose-metabolic proteins that were either up- or downregulated in one of the stress responses. The corresponding single mutants were then grown under the stress treatments and analyzed for their growth and early development (Chapter 2). One isoform among the four sucrose phosphate phosphatases (SPP2) and one fructokinase (FRK) turned out to be essential in seed development, the complete knock-out of them resulted in aborted seed development and non-viable plants. The knock-out mutant of another fructokinase (FRK7), which had been downregulated during the salt-stress treatment, grew slower under normal conditions, but was not further impaired during this stress. Further, a cytosolic… Advisors/Committee Members: Zeeman, Samuel C., Streb, Sebastian, Gibon, Yves.

Subjects/Keywords: info:eu-repo/classification/ddc/570; info:eu-repo/classification/ddc/580; Life sciences; Botanical sciences

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APA (6^th Edition):

Carrera, D. �. (2017). Defining key proteins of the primary carbohydrate metabolism in Arabidopsis thaliana. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/258247

Chicago Manual of Style (16^th Edition):

Carrera, Dániel Árpád. “Defining key proteins of the primary carbohydrate metabolism in Arabidopsis thaliana.” 2017. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/258247.

MLA Handbook (7^th Edition):

Carrera, Dániel Árpád. “Defining key proteins of the primary carbohydrate metabolism in Arabidopsis thaliana.” 2017. Web. 27 Feb 2021.

Vancouver:

Carrera D�. Defining key proteins of the primary carbohydrate metabolism in Arabidopsis thaliana. [Internet] [Doctoral dissertation]. ETH Zürich; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/258247.

Council of Science Editors:

Carrera D�. Defining key proteins of the primary carbohydrate metabolism in Arabidopsis thaliana. [Doctoral Dissertation]. ETH Zürich; 2017. Available from: http://hdl.handle.net/20.500.11850/258247

ETH Zürich

19. Aponte, Eduardo A. Translational methods and models for computational psychiatry.

Degree: 2018, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/274211

► Computational psychiatry is a novel field devoted to improving the understanding and treatment of psychiatric disorders through quantitative methods. A significant part of this endeavour… (more)

Subjects/Keywords: info:eu-repo/classification/ddc/610; info:eu-repo/classification/ddc/570; Medical sciences, medicine; Life sciences

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APA (6^th Edition):

Aponte, E. A. (2018). Translational methods and models for computational psychiatry. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/274211

Chicago Manual of Style (16^th Edition):

Aponte, Eduardo A. “Translational methods and models for computational psychiatry.” 2018. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/274211.

MLA Handbook (7^th Edition):

Aponte, Eduardo A. “Translational methods and models for computational psychiatry.” 2018. Web. 27 Feb 2021.

Vancouver:

Aponte EA. Translational methods and models for computational psychiatry. [Internet] [Doctoral dissertation]. ETH Zürich; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/274211.

Council of Science Editors:

Aponte EA. Translational methods and models for computational psychiatry. [Doctoral Dissertation]. ETH Zürich; 2018. Available from: http://hdl.handle.net/20.500.11850/274211

20. Barido-Sottani, Joëlle. Complex birth-death models for Bayesian phylodynamic inferences.

Degree: 2018, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/308809

► Phylogenetic trees show the evolutionary relationships between individuals, populations or species and are generally built from genetic sequences. Phylodynamic inference focuses on reconstructing the underlying… (more)

▼ Phylogenetic trees show the evolutionary relationships between individuals, populations or species and are generally built from genetic sequences. Phylodynamic inference focuses on reconstructing the underlying evolutionary processes from a phylogenetic tree, and can infer biologically meaningful parameters such as the rate of transmission of a pathogen or the rate of extinction of certain species. Its applications thus range from tracking the spread of epidemics to evaluating the impact of environmental conditions on the diversification process. Birth-death models are one of the main categories of models used for phylodynamic inference. This thesis presents work realized on two important types of birth-death models, the multi-state model for structured populations and the fossilized birth-death process. Chapter 1 presents an overview of Bayesian phylodynamic inference and its applications as well as birth-death models. In Chapter 2, I introduce a new multi-state birth-death (MSBD) model which can be used to study variations in birth and death rates across a phylogenetic tree. I show that this model can reliably infer these rates on both simulated and empirical datasets. Chapter 3 shows an application of the MSBD model to the detection of transmission clusters in HIV transmission networks, for which I show that it performs better than existing cutpoint-based methods. Chapter 4 presents an R package for simulating fossil and taxonomy datasets, which can be used to test and validate existing or future birth-death models integrating fossils. An application of this package is shown in Chapter 5, where I compare several different methods of handling fossil age uncertainty and evaluate their impact on the accuracy of the estimates. In particular, I show that commonly used methods of simplifying the data by disregarding the age uncertainty lead to strong biases in the resulting inference. In Chapter 6, I present a series of workshops and an online knowledge repository I have contributed to, which are designed to help users of Bayesian phylodynamic inference via the software BEAST2 make the best choices for their own datasets. Indeed, as more complex models are developed, communication between users and developers is increasingly crucial. Finally, in Chapter 7, I discuss the methods developed in this thesis and suggest directions for future research. Advisors/Committee Members: Stadler, Tanja, Drummond, Alexei, Salzburger, Walter.

Subjects/Keywords: info:eu-repo/classification/ddc/510; info:eu-repo/classification/ddc/570; Mathematics; Life sciences

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APA (6^th Edition):

Barido-Sottani, J. (2018). Complex birth-death models for Bayesian phylodynamic inferences. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/308809

Chicago Manual of Style (16^th Edition):

Barido-Sottani, Joëlle. “Complex birth-death models for Bayesian phylodynamic inferences.” 2018. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/308809.

MLA Handbook (7^th Edition):

Barido-Sottani, Joëlle. “Complex birth-death models for Bayesian phylodynamic inferences.” 2018. Web. 27 Feb 2021.

Vancouver:

Barido-Sottani J. Complex birth-death models for Bayesian phylodynamic inferences. [Internet] [Doctoral dissertation]. ETH Zürich; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/308809.

Council of Science Editors:

Barido-Sottani J. Complex birth-death models for Bayesian phylodynamic inferences. [Doctoral Dissertation]. ETH Zürich; 2018. Available from: http://hdl.handle.net/20.500.11850/308809

ETH Zürich

21. Manjarrez-Casas, Alejandra M. Effects of antibiotics on individual bacterial cells.

Degree: 2018, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/309075

► While antibiotics are a mainstay of contemporary medicine, many basic questions about how they inactivate and kill bacteria are still unresolved. The main goal of… (more)

▼ While antibiotics are a mainstay of contemporary medicine, many basic questions about how they inactivate and kill bacteria are still unresolved. The main goal of this thesis was to address some of these questions. Specifically, we aimed at expanding our understanding of two central themes that are difficult to explore in traditional microbiological approaches. The first theme is about how antibiotics affect the basic components of bacterial growth: cell division and death. We exposed bacterial populations to various concentrations of antibiotics and analyzed how the population growth patterns that we observed emerged from the interplay between cell division and cell death. The second theme is non-genetic factors that contribute to differences in the response and survival to antibiotics, either between individual cells or between environments with plenty or limited resources. We used Escherichia coli and ribosome-binding antibiotics as our model systems and employed microfluidics and time-lapse microscopy to investigate the effects of antibiotics at the level of individual cells. In Chapter 2, we addressed the effect of antibiotic pulses on bacterial cells. We focused on a range of antibiotic doses where, in batch experiments, a net positive or negative population growth rate would mask death or division rates, respectively. Our single-cell approach allowed us to quantify the division events occurring for each cell. This revealed that antibiotics around what is considered the minimal inhibitory concentrations (MIC) in batch experiments or higher sometimes have no discernible effect on the rate of cell division during the pulse. Informed by this finding and in combination with bulk experiments, we explored the role of time, concentration and total dose (the product of time and concentration) on the probability that bacterial cells would survive an antibiotic pulse. One of our main observations was that total dose had the strongest effect on cell survival, but short pulses of high concentrations or long pulses of low concentrations led to slightly higher mortality than equivalent total doses of intermediate duration and concentration. In Chapter 3, we asked whether we would be able to predict that a given bacterial cell would survive a pulse of antibiotic, based on features of this cell that we could measure previous, during and immediately after antibiotic exposure. We did not find evidence that the interdivision time previous to exposure (as a proxy for growth rate) neither the time that had elapsed since the last division before the pulse (as a proxy for cell cycle position at the onset of the stress) predicted cell fate. We found, however, that potential persisters (cells not dividing at all in the time monitored previous to exposure) showed higher chances of survival in conditions with high mortality. We also found that cell division patterns immediately after the pulse can predict survival. In Chapter 4 we investigated how two different ribosome-targeting antibiotics… Advisors/Committee Members: Ackermann, Martin, Gunawan, Rudiyanto, Dan I., Andersson, López, Daniel.

Subjects/Keywords: info:eu-repo/classification/ddc/610; info:eu-repo/classification/ddc/570; Medical sciences, medicine; Life sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Manjarrez-Casas, A. M. (2018). Effects of antibiotics on individual bacterial cells. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/309075

Chicago Manual of Style (16^th Edition):

Manjarrez-Casas, Alejandra M. “Effects of antibiotics on individual bacterial cells.” 2018. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/309075.

MLA Handbook (7^th Edition):

Manjarrez-Casas, Alejandra M. “Effects of antibiotics on individual bacterial cells.” 2018. Web. 27 Feb 2021.

Vancouver:

Manjarrez-Casas AM. Effects of antibiotics on individual bacterial cells. [Internet] [Doctoral dissertation]. ETH Zürich; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/309075.

Council of Science Editors:

Manjarrez-Casas AM. Effects of antibiotics on individual bacterial cells. [Doctoral Dissertation]. ETH Zürich; 2018. Available from: http://hdl.handle.net/20.500.11850/309075

ETH Zürich

22. Radivojevic, Milos. From selective stimulation to single-spike detection: interfacing neocortical neurons with thousands of microelectrodes at subcellular spatial resolution.

Degree: 2016, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/181050

► Complex operations performed by neuronal networks arise from the orchestrated activities of individual neurons. Therefore, an experimental ability to simultaneously observe and elicit activity in… (more)

▼ Complex operations performed by neuronal networks arise from the orchestrated activities of individual neurons. Therefore, an experimental ability to simultaneously observe and elicit activity in individual neurons over extended periods of time is a prerequisite for exploring how neural circuits work. Recent advances in microelectronics and microfabrication technology have produced novel high-density microelectrode arrays (HD-MEAs) that enable measuring and stimulating in vitro neuronal activity across thousands of microelectrodes noninvasively. The arrays’ dense arrangements of microelectrodes provide hundreds of locations to comprehensively access the electrical activity of a single neuron. The microelectrodes can simultaneously observe and elicit activities in virtually any neuron within the network. However, selectively targeting a specific neuron and not its neighbors and extracting the small signals of a cell’s neurites from the background noise both pose difficult challenges that must be overcome. With this in mind, the first part of this thesis presents strategies for the electrical identification and selective stimulation of individual neurons within cortical networks. The second part describes a method for observing the small individual action potentials (APs), importantly without the need to average multiple events, emitted by the hundreds of micrometers long axonal arbors. The combination of these techniques enables precisely controlling and observing electrical activity across an entire neuron and, thereby, allows for influencing and monitoring how targeted neurons operate within the network. In the first project, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, with the aim to correlate a neuron’s responsiveness to extracellular stimulation to the morphology and electrical characteristics of its various subcellular compartments. We developed strategies to electrically identify any neuron in the network, while subcellular-spatial-resolution recording of extracellular AP traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. We proposed analytical approaches to reveal correlations between spatiotemporal features of extracellular APs and effective stimulation voltages, and explored the limits of targeted extracellular stimulation of different neuronal compartments. We found that stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs. Approaches established in the first project were used to develop a method to non-invasively detect single action potentials throughout the whole axonal arbor of individual cortical neurons. The method was then used to measure (I) the precision of… Advisors/Committee Members: Hierlemann, Andreas, id_orcid0000-0002-3838-2468, Helmchen, Fritjof, Bakkum, Douglas.

Subjects/Keywords: info:eu-repo/classification/ddc/610; info:eu-repo/classification/ddc/570; Medical sciences, medicine; Life sciences

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APA (6^th Edition):

Radivojevic, M. (2016). From selective stimulation to single-spike detection: interfacing neocortical neurons with thousands of microelectrodes at subcellular spatial resolution. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/181050

Chicago Manual of Style (16^th Edition):

Radivojevic, Milos. “From selective stimulation to single-spike detection: interfacing neocortical neurons with thousands of microelectrodes at subcellular spatial resolution.” 2016. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/181050.

MLA Handbook (7^th Edition):

Radivojevic, Milos. “From selective stimulation to single-spike detection: interfacing neocortical neurons with thousands of microelectrodes at subcellular spatial resolution.” 2016. Web. 27 Feb 2021.

Vancouver:

Radivojevic M. From selective stimulation to single-spike detection: interfacing neocortical neurons with thousands of microelectrodes at subcellular spatial resolution. [Internet] [Doctoral dissertation]. ETH Zürich; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/181050.

Council of Science Editors:

Radivojevic M. From selective stimulation to single-spike detection: interfacing neocortical neurons with thousands of microelectrodes at subcellular spatial resolution. [Doctoral Dissertation]. ETH Zürich; 2016. Available from: http://hdl.handle.net/20.500.11850/181050

23. Ulmer, Nicole. Continuous Reaction and Separation of IgG.

Degree: 2019, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/357511

► Biopharmaceuticals are the fastest growing eld in the pharmaceutical sector. Among them, sca olds derived from the classical biopharmaceuticals, such as antibody drug conjugates, antibody… (more)

▼ Biopharmaceuticals are the fastest growing eld in the pharmaceutical sector. Among them, sca olds derived from the classical biopharmaceuticals, such as antibody drug conjugates, antibody fragments and PEGylated proteins, gain increasing attention. These are often derived from an already available product with the aim to give it new functionalities. This reaction is done in a step subsequent to the protein expression in cells. While continuous integrated biomanufacturing is an intensely discussed topic for the production of classical biopharmaceuticals, these alternative sca olds are left aside. Nevertheless, their production would bene t from the advantages of intensi ed processing, like robustness and improved economic performance. In this work we have a look into three di erent case studies dealing with the integration of the reaction and the subsequent separation. In the rst part, literature on the reaction of proteins with functionalized PEG is reviewed. PEGylation increases the blood circulation half-life time, which is an important factor for the drug administration frequency and ultimately for treatment convenience. The standard process consists of a batch reactor followed by a chromatographic puri cation. Innovative processes are introduced that have the aim to increase the selectivity of the reaction. This is relevant as the protein is a valuable reagent and a conversion to only the target product decreases the overall costs. Several process implementations with the reaction both in liquid phase and on a solid support are described and their assets and disadvantages are discussed. The second part is about the conjugation of an antibody with a small molecule. The idea is to have a model system for the synthesis of an antibody drug conjugate, which are potent drugs combining cytotoxic small molecules with the targeting abilities of antibodies. Here, a dye was used as conjugation partner due to safety and analytics. The dye has a reactive succinimidyl ester group, which conjugates primary amines on the surface of the antibody. The reaction was rst studied in both liquid and adsorbed state. With the results, a reactive multi-column countercurrent solvent gradient process was performed, in which the antibody reacts to the mono-conjugate, and simultaneously the product is separated from unconjugated protein. The process requires three columns. On one of these three, the reaction is carried out at all times. The process was run for 23 hours in total and 17 hours in a cyclic steady state. In the third part, a study on the digestion of an antibody into its Fab and Fc fragments is presented. Fab is a valuable fragment as it constitutes the part of the antibody with targeting capabilities. A tubular reactor containing papain bound on agarose was used for the fragmentation. The reaction conditions were studied at di erent temperatures and residence times. During the thesis, it was found that Fab is further digested, leading to smaller fragments. The reactor operation was … Advisors/Committee Members: Morbidelli, Massimo, de Mello, Andrew.

Subjects/Keywords: info:eu-repo/classification/ddc/570; info:eu-repo/classification/ddc/610; Life sciences; Medical sciences, medicine

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APA (6^th Edition):

Ulmer, N. (2019). Continuous Reaction and Separation of IgG. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/357511

Chicago Manual of Style (16^th Edition):

Ulmer, Nicole. “Continuous Reaction and Separation of IgG.” 2019. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/357511.

MLA Handbook (7^th Edition):

Ulmer, Nicole. “Continuous Reaction and Separation of IgG.” 2019. Web. 27 Feb 2021.

Vancouver:

Ulmer N. Continuous Reaction and Separation of IgG. [Internet] [Doctoral dissertation]. ETH Zürich; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/357511.

Council of Science Editors:

Ulmer N. Continuous Reaction and Separation of IgG. [Doctoral Dissertation]. ETH Zürich; 2019. Available from: http://hdl.handle.net/20.500.11850/357511

ETH Zürich

24. Qi, Chao. Molecular architecture of Adenylyl cyclase-based signal transduction complex.

Degree: 2019, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/369504

► Membrane-integral adenylyl cyclases (ACs) are key enzymes in mammalian G protein- dependent signal transduction, which is important in many cellular processes. Signals received by the… (more)

▼ Membrane-integral adenylyl cyclases (ACs) are key enzymes in mammalian G protein- dependent signal transduction, which is important in many cellular processes. Signals received by the G protein-coupled receptors are conveyed to adenylyl cyclases through G proteins, modulating the levels of cellular cyclic adenosine monophosphate (cAMP). Until now, the structural biology studies of adenylyl cyclase have been limited to crystal structures of the chimeric soluble domains of these enzymes. The function of the transmembrane (TM) domain and the detailed catalysis mechanism of the adenylyl cyclases have remained a mystery. My PhD project was aimed at determination of the full-length structure of adenylyl cyclase and adenylyl cyclase-based signal transduction complexes and elucidation of their molecular mechanisms of catalysis and regulation. In the first part of my PhD project (chapter 3), using cryo-electron microscopy (cryo-EM), I determined the first full-length structure of the mammalian membrane adenylyl cyclase AC9 bound to an activated G protein as subunit at 3.4 Å resolution. I found that AC9 is sensitive to forskolin after activation by Gas, based on biochemical assays. The structure revealed the organization of the transmembrane domain and the helical domain that connects the membrane and catalytic domains of AC9. The C-terminal extension of the catalytic domain occludes both the catalytic and the allosteric sites of AC9, inducing a conformation distinct from the substrate- and activator-bound state, suggesting a regulatory role in cAMP production. I determined the structure of a truncated AC9, AC91250, in complex with Gas, forskolin and MANT-GTP. This structure confirmed the existence of the occluded state of AC9. By comparing the AC9-Gas and AC91250-Gas-forskolin-MANT-GTP, we could determine the differences in the conformations of these two structures. The manuscript describing these results has been published in Science. In the second of part of my PhD project (chapter 4), I determined the structure of AC1250-Gas in MANT-GTP bound state. The structure of AC1250-Gas-MANT-GTP provided further insights into the substrate-bound and occluded state of AC9. Comparisons of all available structures showed the conformational changes induced by forskolin. In addition, in collaboration with the group of Andreas Pluckthun (University of Zurich) we developed an artificial AC9 binding protein, DARPin-C4, capable of activating AC9 (chapter 5). We determined the cryo-EM structure of AC9-C4 complex and showed that C4 uses a binding site and activation mechanism similar to that of Gas. In conclusion, combining methods of biochemistry and structural biology I systematically studied the structure and function of a central enzyme in mammalian signal transduction, the membrane AC (AC9) and its complex with Gas protein. This work allowed us to propose the mechanism of forskolin and Gas activation. These results, together with the new tools that I developed in the course of my PhD project (such as the DARPin C4), will not only be… Advisors/Committee Members: Korkhov, Volodymyr M., Pilhofer, Martin, Veprintsev, Dmitry, Danev, Radostin.

Subjects/Keywords: structural biology; info:eu-repo/classification/ddc/570; info:eu-repo/classification/ddc/5; Life sciences; Science

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APA (6^th Edition):

Qi, C. (2019). Molecular architecture of Adenylyl cyclase-based signal transduction complex. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/369504

Chicago Manual of Style (16^th Edition):

Qi, Chao. “Molecular architecture of Adenylyl cyclase-based signal transduction complex.” 2019. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/369504.

MLA Handbook (7^th Edition):

Qi, Chao. “Molecular architecture of Adenylyl cyclase-based signal transduction complex.” 2019. Web. 27 Feb 2021.

Vancouver:

Qi C. Molecular architecture of Adenylyl cyclase-based signal transduction complex. [Internet] [Doctoral dissertation]. ETH Zürich; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/369504.

Council of Science Editors:

Qi C. Molecular architecture of Adenylyl cyclase-based signal transduction complex. [Doctoral Dissertation]. ETH Zürich; 2019. Available from: http://hdl.handle.net/20.500.11850/369504

ETH Zürich

25. Flores Tinoco, Carlos Eduardo. Determination of essential mechanisms in rhizobia that sustain free-living conditions and a functional nitrogen-fixing symbiosis with legumes.

Degree: 2020, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/409308

► Rhizobia are soil-bacteria known by their remarkable ability to thrive as oligotrophs and establish agriculturally important nitrogen-fixing symbiosis with leguminous plants. As part of this… (more)

▼ Rhizobia are soil-bacteria known by their remarkable ability to thrive as oligotrophs and establish agriculturally important nitrogen-fixing symbiosis with leguminous plants. As part of this sophisticated lifestyle, rhizobia must survive and proliferate in the dynamic soil environment before engaging in symbiosis. Symbiosis is characterized by a dramatic number of developmental steps that will allow rhizobia to proliferate inside the legume, in root organs termed nodules. As an endosymbiont, rhizobia will develop into nitrogen-fixing bacteroids capable of converting atmospheric nitrogen into ammonia for the plant. In return, the legume will provide nutrients and a safe space to proliferate. The capacity to rapidly respond to changes within their environment and colonize their legume host has been crucial for the evolutionary success of rhizobia. Accordingly, throughout their evolutionary history, rhizobia have acquired a myriad of gene functions that allow them to cope with the environment. Thus, rhizobia have become a unique model to address how organisms adapt to the environment and establish beneficial interactions with their community. We addressed how rhizobia manage to thrive as oligotrophic soil bacteria. Through a systemswide genetic approach based on Tn5 transposon sequencing (TnSeq) in the rhizobial model Sinorhizobium meliloti, we uncovered the complete set of essential genes for growth under variations in nutrient availability. We identified that from the large genome of S. meliloti (6128 genes), only 5.14% (320 essential genes) encode the most fundamental processes. Moreover, we found that these core-essential genes serve as a molecular chassis on which essential components for specific conditions build on top, hence, reflecting the extensive genomic arsenal that rhizobia have. Furthermore, we show that S. meliloti adapts its cell cycle regulation as a result of the nutrients present in the media. Our results provide novel insights into the mechanisms used by rhizobia to persist as rhizosphere inhabitants. Fixed nitrogen produced during the legume-rhizobia symbiosis is fundamental for the plant to survive and colonize habitats where nitrogen is limiting. However, biological nitrogen fixation is a costly process. Therefore, the plant must provide enough resources to drive this process. Nevertheless, the metabolic network that sustains nitrogen fixation remained to be conclusively determined. Using a systems-biology approach that combined metabolomics and TnSeq, we revealed that, in addition to dicarboxylic acids (i.e. succinate), legumes provide arginine as part of the nutrient exchange between symbionts. Moreover, we show that the co-catabolism of arginine and succinate is sufficient to drive the energy-intensive process of nitrogen fixation. We found that arginine is consumed through a highly redundant and intricate network that connects arginine degradation with energy metabolism and nitrogen fixation. As a result, the plant receives up to 25% more nitrogen compared to… Advisors/Committee Members: Christen, Beat, Fischer, Hans-Martin, Masson-Boivin, Catherine.

Subjects/Keywords: info:eu-repo/classification/ddc/570; info:eu-repo/classification/ddc/630; Life sciences; Agriculture

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APA (6^th Edition):

Flores Tinoco, C. E. (2020). Determination of essential mechanisms in rhizobia that sustain free-living conditions and a functional nitrogen-fixing symbiosis with legumes. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/409308

Chicago Manual of Style (16^th Edition):

Flores Tinoco, Carlos Eduardo. “Determination of essential mechanisms in rhizobia that sustain free-living conditions and a functional nitrogen-fixing symbiosis with legumes.” 2020. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/409308.

MLA Handbook (7^th Edition):

Flores Tinoco, Carlos Eduardo. “Determination of essential mechanisms in rhizobia that sustain free-living conditions and a functional nitrogen-fixing symbiosis with legumes.” 2020. Web. 27 Feb 2021.

Vancouver:

Flores Tinoco CE. Determination of essential mechanisms in rhizobia that sustain free-living conditions and a functional nitrogen-fixing symbiosis with legumes. [Internet] [Doctoral dissertation]. ETH Zürich; 2020. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/409308.

Council of Science Editors:

Flores Tinoco CE. Determination of essential mechanisms in rhizobia that sustain free-living conditions and a functional nitrogen-fixing symbiosis with legumes. [Doctoral Dissertation]. ETH Zürich; 2020. Available from: http://hdl.handle.net/20.500.11850/409308

ETH Zürich

26. Poljak, Kristina. N-Linked Protein Glycosylation. Functional characterization of the eukaryotic oligosaccharyltransferases.

Degree: 2017, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/182693

► N-linked protein glycosylation is a highly conserved and an essential protein modification found throughout the three domains of life. In animal, plants and fungi the… (more)

▼ N-linked protein glycosylation is a highly conserved and an essential protein modification found throughout the three domains of life. In animal, plants and fungi the preassembled oligosaccharide consisting of two N-acetylglucosamines, nine mannoses and three glucoses is transferred en bloc from the lipid carrier to the asparagine side chains within N-X-S/T consensus sequences on nascent polypeptides in the lumen of the endoplasmic reticulum (ER). This transfer is catalysed by the central enzyme of the pathway, oligosaccharyltransferase (OST). After the transfer, the oligosaccharide is modified in a species, tissue and cell-specific manner, resulting in a vast array of different glycan structures. The first chapter of this thesis offers an overview of the N-linked protein glycosylation pathway. The biosynthesis of the lipid-linked oligosaccharide (LLO) is described first followed by the description of the OST and the biological relevance of this modification. Furthermore, diverse analytical tools and methods used to help explore and characterize the pathway, with the emphasis on the quantitative mass spectrometric approaches, are discussed. In the second chapter, we coupled parallel reaction monitoring (PRM) mass spectrometry method to stable isotope labelling (SILAC) to measure N-linked glycosylation occupancy of yeast glycoproteins. The OST from yeast Saccharomyces cerevisiae is a multi-subunit protein complex. Using our SILAC-PRM method, we further explored the roles of the two non-essential OST subunits, Ost3p and Ost6p, and provided insights into the mechanisms that regulate site-specific N-glycosylation by the OST. The investigation of the substrate specificity of the single subunit OSTs from Trypanosoma brucei is reported in chapter three. The effect of different oligosaccharide substrate structures on the function of TbOSTs was studied in yeast using genetic manipulations of the LLO biosynthesis. Additionally, structure to function coupled to SILAC-PRM analyses were performed to identify regions in the OST proteins that influence the specificity of different paralogues for the LLO as well as for the polypeptide substrate. In order to functionally characterize WBP1, an essential subunit of yeast OST, we performed a mutagenesis study reported in the fourth chapter. We have used reverse genetics approach for generating point mutations in the conserved residues of Wbp1p and identified novel mutants that alter glycosylation by influencing complex assembly. Concluding remarks and future perspectives complete the thesis in the fifth chapter. Advisors/Committee Members: Aebi, Markus, Locher, Kaspar, Yves Barral, /.

Subjects/Keywords: N-linked glycosylation; info:eu-repo/classification/ddc/570; Life sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Poljak, K. (2017). N-Linked Protein Glycosylation. Functional characterization of the eukaryotic oligosaccharyltransferases. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/182693

Chicago Manual of Style (16^th Edition):

Poljak, Kristina. “N-Linked Protein Glycosylation. Functional characterization of the eukaryotic oligosaccharyltransferases.” 2017. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/182693.

MLA Handbook (7^th Edition):

Poljak, Kristina. “N-Linked Protein Glycosylation. Functional characterization of the eukaryotic oligosaccharyltransferases.” 2017. Web. 27 Feb 2021.

Vancouver:

Poljak K. N-Linked Protein Glycosylation. Functional characterization of the eukaryotic oligosaccharyltransferases. [Internet] [Doctoral dissertation]. ETH Zürich; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/182693.

Council of Science Editors:

Poljak K. N-Linked Protein Glycosylation. Functional characterization of the eukaryotic oligosaccharyltransferases. [Doctoral Dissertation]. ETH Zürich; 2017. Available from: http://hdl.handle.net/20.500.11850/182693

27. Weisser, Melanie. Structural Insights into Eukaryotic Translation Initiation and Re-Initiation.

Degree: 2017, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/185232

► During protein synthesis, the genetic information is translated into a sequence of amino acid building blocks that are sequentially attached to each other by a… (more)

▼ During protein synthesis, the genetic information is translated into a sequence of amino acid building blocks that are sequentially attached to each other by a large ribonucleoprotein complex, the ribosome. One triplet of nucleotides translates into one amino acid. The eukaryotic ribosome can be divided into a small (40S) and a large (60S) subunit. Protein translation is initiated on the small ribosomal subunit upon forming a complex with initiator transfer RNA (tRNA) carrying the first amino acid and messenger RNA (mRNA) containing the nucleotide sequence template. During canonical initiation, the eukaryotic small ribosomal subunit binds to the mRNA in proximity of the capped 5' end. From there it scans along the mRNA until it reaches the correct initiation site for translation where the protein-coding sequence starts. Binding of the initiator tRNA to the start codon on the mRNA determines the reading frame for translation. Once the start codon has been identified correctly, the large ribosomal subunit joins the complex and translation can proceed. All of the above steps are highly regulated and require accessory translation initiation factors as regulatory proteins or regulatory mRNA sequences. In eukaryotes, canonical translation initiation involves at least 12 translation initiation factors (eIF). Two of them, eIF1 and eIF1A, are critical for the fidelity of start codon recognition and for the recruitment of the initiator tRNA to the complex. eIF1 dissociates upon start codon binding, while eIF1A is also important for the association with the large ribosomal subunit at a later stage. In the first part of this thesis, a 3.7 A resolution crystal structure of the canonical eukaryotic 40S-eIF1A-eIF1 initiation complex is described. The structure revealed how the two initiation factors bind to the small ribosomal subunit, how they are positioned with respect to each other and how they influence the conformation of the 40S subunit. The visualization of structural features of the two initiation factors and the conformational changes observed in the decoding center of the small ribosomal subunit provided new insights into the mechanisms of scanning and start codon recognition during eukaryotic translation initiation. In recent years, it became obvious that special sequence motifs or secondary structure elements within the mRNA sequence upstream of the start codon can influence the translation initiation efficiency at the downstream protein-coding open reading frame, allowing an additional level for regulating eukaryotic translation. Approximately half of the mammalian mRNAs possess one or more short upstream open reading frames (uORF), which do not encode for proteins, but regulate the translation efficiency at the downstream main open reading frame. In such a context, translation is terminated at the uORF, but instead of being released, the ribosome remains associated with the mRNA and "re-initiates" translation at the downstream main ORF. In many cases, re-initiation can be mediated… Advisors/Committee Members: Ban, Nenad, Leibundgut, Marc, Maier, Timm, Panse, Vikram.

Subjects/Keywords: Translation initiation; info:eu-repo/classification/ddc/570; Life sciences

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APA (6^th Edition):

Weisser, M. (2017). Structural Insights into Eukaryotic Translation Initiation and Re-Initiation. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/185232

Chicago Manual of Style (16^th Edition):

Weisser, Melanie. “Structural Insights into Eukaryotic Translation Initiation and Re-Initiation.” 2017. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/185232.

MLA Handbook (7^th Edition):

Weisser, Melanie. “Structural Insights into Eukaryotic Translation Initiation and Re-Initiation.” 2017. Web. 27 Feb 2021.

Vancouver:

Weisser M. Structural Insights into Eukaryotic Translation Initiation and Re-Initiation. [Internet] [Doctoral dissertation]. ETH Zürich; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/185232.

Council of Science Editors:

Weisser M. Structural Insights into Eukaryotic Translation Initiation and Re-Initiation. [Doctoral Dissertation]. ETH Zürich; 2017. Available from: http://hdl.handle.net/20.500.11850/185232

ETH Zürich

28. Müller, Nicola. Global Migration and Transmission Dynamics of Influenza H3N2.

Degree: 2015, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/183147

► Phylogeographic methods have been used extensively to characterize the global migration patterns of in- fluenza. Those methods however make strong assumptions about independence of tree… (more)

Subjects/Keywords: phylogeography; influenza; info:eu-repo/classification/ddc/570; Life sciences

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APA (6^th Edition):

Müller, N. (2015). Global Migration and Transmission Dynamics of Influenza H3N2. (Thesis). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/183147

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Müller, Nicola. “Global Migration and Transmission Dynamics of Influenza H3N2.” 2015. Thesis, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/183147.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Müller, Nicola. “Global Migration and Transmission Dynamics of Influenza H3N2.” 2015. Web. 27 Feb 2021.

Vancouver:

Müller N. Global Migration and Transmission Dynamics of Influenza H3N2. [Internet] [Thesis]. ETH Zürich; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/183147.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Müller N. Global Migration and Transmission Dynamics of Influenza H3N2. [Thesis]. ETH Zürich; 2015. Available from: http://hdl.handle.net/20.500.11850/183147

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

29. Trombev, Filip. Učinki skladov EU za predpristopno pomoč v Republiki Makedoniji.

Degree: 2019, Univerza v Mariboru

URL: https://dk.um.si/IzpisGradiva.php?id=73159 ; https://dk.um.si/Dokument.php?id=132817&dn= ; https://plus.si.cobiss.net/opac7/bib/13329180?lang=sl

►

Z razvojem je Evropska unija ustvarila različne mehanizme in politike v smeri izvajanja ukrepov, pomoči, zagotavljanja storitev, razvoja, vojaških posegov itd. Skladi Evropske unije predstavljajo… (more)

▼

Z razvojem je Evropska unija ustvarila različne mehanizme in politike v smeri izvajanja ukrepov, pomoči, zagotavljanja storitev, razvoja, vojaških posegov itd. Skladi Evropske unije predstavljajo instrumente ali programe, ki nudijo pomoč državam članicam ali državam kandidatkam za članstvo v razvoju na različnih področjih. Na splošno so skladi oziroma programi namenjeni državam članicam, a za olajšanje njihove priprave na članstvo držav kandidatk je del teh sredstev odprt za države kandidatke ali posebna sredstva zgolj za predpristopno pomoč, ki pa je poseben interes ali namen te raziskave. V skladu s tem smo se pri nadaljnji opredelitvi problema usmerili ravno na Republiko Makedonijo kot državo kandidatko za članstvo v Uniji, s poudarkom na izkoriščenosti na državni ravni. Do danes je več skladov prispevalo ali ponudilo priložnost za podporo državam članicam EU in državam kandidatkam za članstvo. Skladi so eden od instrumentov, ki pomagajo neenakim ali manj razvitim državam doseči razvojno raven tistih, ki so bolj razviti. Skladi so instrumenti, ki v veliki meri prispevajo k olajšanju predpristopne poti kandidatkam predvsem s finančno pomočjo ter pomočjo na številnih področjih, ki so pomembna tako za Unijo kot tudi za države kandidatke. V začetnih poglavjih magistrskega dela smo opredelili Evropsko integracijo, njene cilje in njeno ekonomiko oziroma zakaj se države hočejo integrarati v EU, katere so prednosti in slabosti, izzivi in možnosti, pojasnili smo evolucijo Evropske Unije oziroma, kako je prišlo do politične in ekonomske skupnosti, opredelili sklade za predpristopno pomoč in pojasnili njihove cilje in naloge, opisali sestavine oziroma komponente teh skladov ter na kratko opisali njihovo implementacijo v Republiki Makedoniji. V nadaljevanju smo analizirali izkoriščenost sredstev Instrumenta za predpristopno pomoč na državni ravni, in sicer glede na vrsto pogodb, organ ki vodi posel, vrsto uporabnika, v primerjavi z nacionalno udeležbo. Analizirali smo tudi sredstva glede na osnovne makroekonomske kazalnike ter podali dokaz za postavljeno hipotezo s pomočjo linearne regresije.

With development up until today, the European Union has created various mechanisms in the policies towards the implementation of measures, assistance, provision of services, development, military interventions etc. The European Union funds represent instruments or programs that provide assistance to Member States or candidate countries for membership in the development in various fields. In general, funds or programs are targeted at Member States, but in order to facilitate their preparation for membership of the candidate countries, part of this funding is open to candidate countries or special funds only for pre-accession assistance, which is of particular interest or a purpose of this research and accordingly, further problem-solving was directed towards the Republic of Macedonia as a candidate country for membership in the Union, with emphasis on utilization at the state level. Until today, several funds have contributed or…

Advisors/Committee Members: Boršič, Darja.

Subjects/Keywords: Instrument za predpristopno pomoč; Evropska unija; skladi EU; evropske integracije.; Instrument for pre-accession assistance; European Union; EU funds; European integration.; info:eu-repo/classification/udc/339.923

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Trombev, F. (2019). Učinki skladov EU za predpristopno pomoč v Republiki Makedoniji. (Masters Thesis). Univerza v Mariboru. Retrieved from https://dk.um.si/IzpisGradiva.php?id=73159 ; https://dk.um.si/Dokument.php?id=132817&dn= ; https://plus.si.cobiss.net/opac7/bib/13329180?lang=sl

Chicago Manual of Style (16^th Edition):

Trombev, Filip. “Učinki skladov EU za predpristopno pomoč v Republiki Makedoniji.” 2019. Masters Thesis, Univerza v Mariboru. Accessed February 27, 2021. https://dk.um.si/IzpisGradiva.php?id=73159 ; https://dk.um.si/Dokument.php?id=132817&dn= ; https://plus.si.cobiss.net/opac7/bib/13329180?lang=sl.

MLA Handbook (7^th Edition):

Trombev, Filip. “Učinki skladov EU za predpristopno pomoč v Republiki Makedoniji.” 2019. Web. 27 Feb 2021.

Vancouver:

Trombev F. Učinki skladov EU za predpristopno pomoč v Republiki Makedoniji. [Internet] [Masters thesis]. Univerza v Mariboru; 2019. [cited 2021 Feb 27]. Available from: https://dk.um.si/IzpisGradiva.php?id=73159 ; https://dk.um.si/Dokument.php?id=132817&dn= ; https://plus.si.cobiss.net/opac7/bib/13329180?lang=sl.

Council of Science Editors:

Trombev F. Učinki skladov EU za predpristopno pomoč v Republiki Makedoniji. [Masters Thesis]. Univerza v Mariboru; 2019. Available from: https://dk.um.si/IzpisGradiva.php?id=73159 ; https://dk.um.si/Dokument.php?id=132817&dn= ; https://plus.si.cobiss.net/opac7/bib/13329180?lang=sl

30. Dubuis, Sébastien. Analysis of metabolic activity in breast cancer cell lines via untargeted metabolomics.

Degree: 2017, ETH Zürich

URL: http://hdl.handle.net/20.500.11850/205761

► During tumorigenesis, metabolism of cancer cells is altered and fluxes in central metabolism are rerouted. Under the influence of oncogenes and tumor suppressors that modulate… (more)

▼ During tumorigenesis, metabolism of cancer cells is altered and fluxes in central metabolism are rerouted. Under the influence of oncogenes and tumor suppressors that modulate the expression of multiple enzymes, cancer cells increase fermentative metabolism of glucose to lactate independent of oxygenation, i.e. the so-called Warburg effect. Simultaneously, they activate glutaminolysis, upregulate serine synthesis or deregulate fatty acid synthesis. All these alterations allow cancer cells to grow by providing the essential building blocks necessary for proliferation. Yet, aberrant metabolic activity renders cancer cells more susceptible than normal tissue to drugs that target metabolic enzymes and hence provide potential therapeutic targets. However, the intertwined influences of oncogenes and the tumor’s microenvironment result in large heterogeneity in the metabolic alterations. For this reason, targeting cancer cell metabolism requires methods that allow investigation of intracellular metabolic fluxes. Intracellular metabolic fluxes cannot be measured directly and are inferred indirectly from metabolite levels and in silico models. However, approaches such as 13C metabolic flux analysis (MFA) or flux balance analysis (FBA) are poorly suited to calculate fluxes in mammalian cells or animal models. Alternatively, enzyme centric measurements, such as proteomics or transcriptomics, can be used to monitor the regulatory responses of cells, but fail to reveal the functional outcome, i.e. the impact on the metabolic fluxes. In this thesis, we set out to explore the pertinence of metabolomics as a tool to discover metabolic alterations in cancer cells. By comprehensively measuring the metabolic content of cells, we aim at discovering functional change, i.e. change in the metabolic fluxes. By using both top down (chapter 2) and data-driven (chapter 3 and 4) approaches we provide substantial evidences that changes in the metabolic pools revealed by untargeted metabolomics mirror changes in intracellular fluxes. For thorough investigation of the variability found in the metabolome content of cancer cells, we analyzed the intracellular metabolome of 18 breast cell lines using non-targeted mass spectrometry-based metabolomics in chapter 2. The cell lines were clinically well-characterized in terms of subtypes, which were relevant to breast cancer treatments, but no prior knowledge existed at a metabolic level. The expectations were that the intracellular metabolome of these cell lines is governed by clinical subtypes that are known to broadly affect cellular transcription. Contrary to the expectations, the metabolome patterns were not associated with any of the known clinical classes and we discovered that the cell lines have cell-specific metabolome patterns. To assess whether these patterns can reveal changes in metabolic fluxes, we measured extracellular fluxes and subsequently showed that some metabolic pools indeed correlate with the extracellular fluxes. This indicated that, despite not correlating with clinical… Advisors/Committee Members: Zamboni, Nicola, id_orcid0000-0003-1271-1021, Sauer, Uwe, Claassen, Manfred.

Subjects/Keywords: Cancer; Metabolism; Metabolomics; Breast Cancer; info:eu-repo/classification/ddc/610; info:eu-repo/classification/ddc/570; Medical sciences, medicine; Life sciences

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APA (6^th Edition):

Dubuis, S. (2017). Analysis of metabolic activity in breast cancer cell lines via untargeted metabolomics. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/205761

Chicago Manual of Style (16^th Edition):

Dubuis, Sébastien. “Analysis of metabolic activity in breast cancer cell lines via untargeted metabolomics.” 2017. Doctoral Dissertation, ETH Zürich. Accessed February 27, 2021. http://hdl.handle.net/20.500.11850/205761.

MLA Handbook (7^th Edition):

Dubuis, Sébastien. “Analysis of metabolic activity in breast cancer cell lines via untargeted metabolomics.” 2017. Web. 27 Feb 2021.

Vancouver:

Dubuis S. Analysis of metabolic activity in breast cancer cell lines via untargeted metabolomics. [Internet] [Doctoral dissertation]. ETH Zürich; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/20.500.11850/205761.

Council of Science Editors:

Dubuis S. Analysis of metabolic activity in breast cancer cell lines via untargeted metabolomics. [Doctoral Dissertation]. ETH Zürich; 2017. Available from: http://hdl.handle.net/20.500.11850/205761

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Open Access Theses and Dissertations