Дисертації з теми "Systems Biology, Synthetic Biology, Metabolic Engineering"
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Boyle, Patrick M. "Network-Scale Engineering: Systems Approaches to Synthetic Biology." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10298.
Повний текст джерелаLibis, Vincent. "New inputs for synthetic biological systems." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC127/document.
Повний текст джерелаSynthetic biologists program DNA with the aim of building biological systems that react under certain conditions in a predefined way. This ability could have impact in several fields, from medicine to industrial fermentation. While the scalability of synthetic biological circuits in terms of signal processing in now almost demonstrated, the variety of input signals for these circuits is limited. Because each application typically requires a circuit to react to case-specific molecules, the lack of input diversity is a major obstacle to the development of new applications. Two axis are developed over the course of this thesis to try to address input-related problems. The main axis consists in a new strategy aiming at systematically and immediately increasing the chemical diversity of inputs for synthetic circuits. Current approaches to expand the number of potential inputs focus on re-engineering sensing systems such as riboswitches or allosteric transcription factors to make them react to previously non-detectable molecules. On the contrary, here we developed a method to transform the non-detectable molecules themselves into molecules for which sensing systems already exist. These chemical transformations are realized in situ by expressing synthetic metabolic pathways in the cell. In order to systematize this strategy, we leveraged computer-aided design to predict ways of detecting new molecules by digging into all known biochemical reactions. We then implemented several predictions in vivo that successfully enabled E. coli to detect new chemicals. Aside from the interest of the method for biotechnological applications, this shows that in addition to transferring matter and energy, metabolism can also play a role in transferring information, raising the question of potential occurrences of this sensing strategy in nature. A second axis introduce a way to exempt simple programs from the need for a chemical input, and explore the use of a biological input instead. In situations where a single timely induction or repression of multiple genes is required, such as in industrial fermentation processes, we propose to replace expensive chemical induction by simultaneous infection of all the members of a growing population of cells with viral particles inputting in real-time all the necessary information for the task at hand. In the context of fermentation, we developed engineered viral particles that can dynamically reprogram the metabolism of a large population of bacteria at the optimal stage of growth and force them to produce value-added chemicals
Triana, Dopico Julián. "Model-based analysis and metabolic design of a cyanobacterium for bio-products synthesis." Doctoral thesis, Universitat Politècnica de València, 2014. http://hdl.handle.net/10251/39351.
Повний текст джерелаTriana Dopico, J. (2014). Model-based analysis and metabolic design of a cyanobacterium for bio-products synthesis [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/39351
TESIS
Merrick, Christine. "A synthetic biology approach to metabolic pathway engineering." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/6383/.
Повний текст джерелаTorella, Joseph Peter. "Synthetic biology approaches to bio-based chemical production." Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:13088835.
Повний текст джерелаPedersen, Michael. "Modular languages for systems and synthetic biology." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4602.
Повний текст джерелаMartínez-Klimova, Elena. "Synthetic biology approaches to the metabolic engineering of Geobacillus thermoglucosidans for isobutanol production." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/45409.
Повний текст джерелаCampodonico, Alt Miguel Ángel. "Systems biology and chemoinformatics methods for biomining and systems metabolic engineering applications." Tesis, Universidad de Chile, 2014. http://repositorio.uchile.cl/handle/2250/132047.
Повний текст джерелаIn the first chapter, this thesis aims to demonstrate the great potential of Constraint-Based Reconstruction and Analysis (COBRA) methods for studying and predicting specific phenotypes in the bacterium Acidithiobacillus ferrooxidans. A genome-scale metabolic reconstruction of Acidithiobacillus ferrooxidans ATCC 23270 (iMC507) is presented and characterized. iMC507 is validated for aerobic chemolithoautotrophic conditions by fixating carbon dioxide and using three different electron donors: ferrous ion, tetrathionate and thiosulfate. Furthermore, the model is utilized for (i) quantitatively studying and analyzing key reactions and pathways involved in the electron transfer metabolism, (ii) describing the central carbon metabolism and (iii) for evaluating the potential to couple the production of extracellular polymeric substances through knock-outs. The second chapter work outlines the effort towards advancing the field of systems metabolic engineering by using COBRA methods in conjunction with chemoinformatic approaches to metabolically engineer the bacterium Escherichia coli. A complete strain design workflow integrating synthetic pathway prediction with growth-coupled designs for the production of non-native compounds in a target organism of interest is outlined. The generated enabling technology is a computational pipeline including chemoinformatics, bioinformatics, constraint-based modeling, and GEMs to aid in the process of metabolic engineering of microbes for industrial bioprocessing purposes. A retrosynthetic based pathway predictor algorithm containing a novel integration with GEMs and reaction promiscuity analysis is developed and demonstrated. Specifically, the production potential of 20 industrially-relevant chemicals in E. coli and feasible designs for production strains generation is outlined. A comprehensive mapping from E. coli s native metabolome to commodity chemicals that are 4 reactions or less away from a natural metabolite is performed. Sets of metabolic interventions, specifically knock-outs and knock-ins that coupled the target chemical production to growth rate were determined. In the third chapter, in order to aid the field of cancer metabolism, potential biomarkers were determined through gain of function oncometabolites predictions. Based on a chemoinformatic approach in conjunction with the global human metabolic network Recon 2, a workflow for predicting potential oncometabolites is constructed. Starting from a list of mutated enzymes genes, described as GoF mutations, a range of promiscuous catalytic activities are inferred. In total 24 chemical substructures of oncometabolites resulting from the GoF analysis are predicted.
McArthur, George Howard IV. "Orthogonal Expression of Metabolic Pathways." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/3087.
Повний текст джерелаHuttanus, Herbert M. "Screening and Engineering Phenotypes using Big Data Systems Biology." Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/102706.
Повний текст джерелаDoctor of Philosophy
Feist, Adam Michael. "Model-driven metabolic engineering of Escherichia coli a systems biology approach /." Diss., [La Jolla] : University of California, San Diego, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p3354731.
Повний текст джерелаTitle from first page of PDF file (viewed June 2, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
Silver, Matthew Robin. "Open collaborative system design : a strategic framework with application to synthetic biology." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/63012.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references (p. 251-259).
Across technology industries and particularly at the cutting edge of biotechnology a debate is under way about the proper balance between open and closed - between co-developing products with shared information and open standards, versus using more traditional, closed, proprietary processes. Beyond the relative success of open source software to date, it is not clear how and whether open design processes might be applied generally for complex, assembled technologies. This problem takes on special urgency within the domain of synthetic biology, an emerging discipline in which many practitioners advocate opening design and development through platforms such as the registry of standardized biological parts. Biotechnology is IP intensive in part because commercialization is complicated and capital intensive. How might one develop a sustainable open development process in this context? This thesis addresses these questions from an Engineering Systems perspective. Defining open, collaborative system development (OCSD) specifically as a process in which subsystems are created voluntarily by an unrestricted set of third-party contributors, it makes the following claim: An OCSD process can itself be designed, with the principal objective of creating an environment for third-party innovation. To support this claim the thesis outlines a conceptual framework to guide OCSD design. The framework includes a taxonomy of parameters and constraints relevant to opening design, a list of options within each taxonomic category, and three high level strategies found to recur as a function of sponsor goals and technological constraints. Finally, the thesis proposes a quantitative method, based on multidisciplinary modeling and pareto analysis, to design open standards within the context of one of the three strategies. The research is carried out through a pragmatic blend of case studies and quantitative modeling. First, an in-depth, multi-discipline literature review synthesizes relevant taxonomic categories. Thirteen examples of OCSD spanning nine industries are then analyzed to define options within each taxonomic category. The case studies are also used to identify strategies for opening design based on correlations between OCSD options. The framework is validated and expanded through an in-depth case study of the opening of Very Large Scale Integration (VLSI) in the semi-conductor industry in the late 1970s. Finally, a quantitative method is developed to guide the design of open standards within one of the three strategies. These three contributions - the framework, correlated strategies, and quantitative method - are then applied to a particular biotechnology called microbial fuel cells.
by Matthew Robin Silver.
Ph.D.
Gowen, Christopher. "Model-Guided Systems Metabolic Engineering of Clostridium thermocellum." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/2529.
Повний текст джерелаCarbonell, Ballestero Max 1988. "Engineering principles for synthetic biology : from concept to practice." Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/385923.
Повний текст джерелаLa Biologia Sintètica és un camp de recerca emergent relativament nou i multi-facètic que combina la biologia amb la tecnologia de formes innovadores i emocionants. Una de les seves principals branques té com a objectiu aconseguir ingenieritzar els sistemes vius des d’abaix de manera racional i senzilla, tal com passa en altres tipus d’enginyeria. La naturalesa inherentment complexa dels éssers vius els converteix en un substrat difícil sobre el qual aplicar principis d’enginyeria com l’abstracció, l’estandardització i la modularitat. S’han dedicat esforços per superar aquestes limitacions i adaptar aquests principis perquè funcionin sobre sistemes vius, tot i que encara que amb un èxit relatiu. L’objectiu d’aquesta tesi és explorar críticament què és la Biologia Sintètica i quan lluny està de ser una veritable enginyeria. En aquesta tesi, primer presentem un article de revisió que explora i discuteix a fons aquest escenari. Després presentem dos treballs que han de contribuir a aquest ambiciós i difícil objectiu. En primer lloc, en el context de l’estandardització, adrecem la necessitat d’una millor caracterització de les parts genètiques oferint un exemple de marc teòric amb fonaments biològics que esta inspirat en teoria enzimològica clàssica. En segon lloc, i relacionat amb el principi de modularitat, oferim un marc teòric, aquest cop inspirat en la llei de Ohm de la teoria elèctrica, que descriu l’aparellament no intencionat de les carregues genètiques coexistents dins d’una cèl.lula hoste qualssevol degut al fet de compartir un conjunt comú limitat de recursos i maquinària cel•lular. Ambdós treballs contribueixen, per un cantó, a incrementar el nostre coneixement sobre els principis d’organització dels éssers vius, i per l’altre, a millorar com s’apliquen els principis d’enginyeria pel disseny de circuits sintètics. Finalment, aquests treballs emfatitzen la necessitat de trobar millors marcs teòrics o models recolzats experimentalment que haurien de permetre’ns fer un salt des de l’actual Biologia Sintètica ad hoc, farregosa i basada en assaig-error, a un tipus d’enginyeria ben establerta que pugui ser tan profitosa i eficient en el reialme dels éssers vius com ho són les altres enginyeries.
Hugie, Michaela R. "Expression Systems for Synthetic Spider Silk Protein Production." DigitalCommons@USU, 2019. https://digitalcommons.usu.edu/etd/7679.
Повний текст джерелаCheckley, Stephen. "Engineering tuneable gene circuits in yeast." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/engineering-tuneable-gene-circuits-in-yeast(71dda344-8802-4862-9b29-1a671f4c96ab).html.
Повний текст джерелаVázquez, Vilar Marta. "DESIGN OF GENETIC ELEMENTS AND SOFTWARE TOOLS FOR PLANT SYNTHETIC BIOLOGY." Doctoral thesis, Universitat Politècnica de València, 2016. http://hdl.handle.net/10251/68483.
Повний текст джерела[ES] La Biología Sintética es un campo emergente de carácter interdisciplinar que se fundamenta en la aplicación de los principios ingenieriles de modularidad, abstracción y estandarización a la ingeniería genética. Una nueva vertiente de la Biología Sintética aplicada a las plantas, la Biología Sintética Vegetal (BSV), ofrece nuevas posibilidades de mejora de cultivos que podrían llevar a una mejora de la resistencia, a una mayor productividad, o a un aumento de la calidad nutricional. Sin embargo, para alcanzar este fin las herramientas moleculares disponibles en estos momentos para BSV deben ser adaptadas para convertirse en modulares, estándares y más precisas. Por ello se planteó como objetivo general de esta Tesis adaptar, expandir y refinar las herramientas de ensamblaje de DNA de la BSV para permitir la incorporación de especificaciones funcionales en la descripción de elementos genéticos estándar (fitobricks) y facilitar la construcción de estructuras multigénicas cada vez más complejas y precisas, incluyendo herramientas de editado genético. El punto de partida de esta Tesis fue el método de ensamblaje modular de ADN GoldenBraid (GB) basado en enzimas de restricción tipo IIS. Para optimizar el proceso de ensamblaje y catalogar la colección de fitobricks generados se desarrollaron una base de datos y un conjunto de herramientas software, tal y como se describe en el Capítulo 1. El paquete final de software se presentó en formato web como GB2.0, haciéndolo accesible al público a través de www.gbcloning.upv.es. El Capítulo 1 también proporciona una descripción detallada del funcionamiento de GB2.0 ejemplificando su uso con el ensamblaje de una construcción multigénica para la producción de antocianinas. Con el aumento en número y complejidad de las construcciones GB, el siguiente paso necesario fue el refinamiento de los estándar con la incorporación de la información experimental asociada a cada elemento genético (se describe en el Capítulo 2). Para este fin, el paquete de software de GB se reformuló en una nueva versión (GB3.0), un sistema de ensamblaje auto-contenido y completamente trazable en el que los datos experimentales que describen la funcionalidad de cada elemento genético se muestran en forma de una hoja de datos estándar. La utilidad de las especificaciones técnicas para anticipar el comportamiento de dispositivos biológicos compuestos se ejemplificó con la combinación de un interruptor químico y un prototipo de un módulo de sobreproducción de antocianinas equivalente al descrito en el Capítulo 1, resultando en un dispositivo de producción de antocianinas con respuesta a dexametasona. Además, en el Capítulo 3 se describe la adaptación a la tecnología GB de las herramientas de ingeniería genética CRISPR/Cas9, así como su caracterización funcional. La funcionalidad de estas herramientas para editado génico y activación y represión transcripcional se validó con el sistema de expresión transitoria en N.benthamiana. Finalmente, el Capítulo 4 presenta una implementación práctica del uso de la tecnología GB para hacer mejora vegetal de manera precisa. La transformación estable en tomate de una construcción intragénica que comprendía un marcador de selección intragénico y un regulador de la biosíntesis de flavonoides resultó en frutos con un mayor contenido de flavonoles. En conjunto, esta Tesis muestra la implementación de diseños genéticos cada vez más complejos y precisos en plantas utilizando elementos estándar y herramientas modulares siguiendo los principios de la Biología Sintética.
[CAT] La Biologia Sintètica és un camp emergent de caràcter interdisciplinar que es fonamenta amb l'aplicació a la enginyeria genètica dels principis de modularitat, abstracció i estandarització. Una nova vessant de la Biologia Sintètica aplicada a les plantes, la Biologia Sintètica Vegetal (BSV), ofereix noves possibilitats de millora de cultius que podrien portar a una millora de la resistència, a una major productivitat, o a un augment de la qualitat nutricional. Tanmateix, per poder arribar a este fi les eines moleculars disponibles en estos moments per a la BSV han d'adaptar-se per convertir-se en modulars, estàndards i més precises. Per això es plantejà com objectiu general d'aquesta Tesi adaptar, expandir i refinar les eines d'ensamblatge d'ADN de la BSV per permetre la incorporació d'especificacions funcionals en la descripció d'elements genètics estàndards (fitobricks) i facilitar la construcció d'estructures multigèniques cada vegada més complexes i precises, incloent eines d'edidat genètic. El punt de partida d'aquesta Tesi fou el mètode d'ensamblatge d'ADN modular GoldenBraid (GB) basat en enzims de restricció tipo IIS. Per optimitzar el proces d'ensamblatge i catalogar la col.lecció de fitobricks generats es desenvolupà una base de dades i un conjunt d'eines software, tal i com es descriu al Capítol 1. El paquet final de software es presentà en format web com GB2.0, fent-se accessible al públic mitjançant la pàgina web www.gbcloning.upv.es. El Capítol 1 també proporciona una descripció detallada del funcionament de GB2.0, exemplificant el seu ús amb l'ensamblatge d'una construcció multigènica per a la producció d'antocians. Amb l'augment en nombre i complexitat de les construccions GB, el següent pas fou el refinament dels estàndards amb la incorporació de la informació experimental associada a cada element genètic (es descriu en el Capítol 2). Per a aquest fi, el paquet de software de GB es reformulà amb una nova versió anomenada GB3.0. Aquesta versió consisteix en un sistema d'ensamblatge auto-contingut i complemtament traçable on les dades experimentals que descriuen la funcionalitat de cada element genètic es mostren en forma de fulla de dades estàndard. La utilitat de les especificacions tècniques per anticipar el comportament de dispositius biològics compostos s'exemplificà amb la combinació de un interruptor químic i un prototip d'un mòdul de sobreproducció d'antocians equivalent al descrit al Capítol 1. Aquesta combinació va tindre com a resultat un dispositiu de producció d'antocians que respón a dexametasona. A més a més, al Capítol 3 es descriu l'adaptació a la tecnologia GB de les eines d'enginyeria genètica CRISPR/Cas9, així com la seua caracterització funcional. La funcionalitat d'aquestes eines per a l'editat gènic i activació i repressió transcripcional es validà amb el sistema d'expressió transitòria en N. benthamiana. Finalment, al Capítol 4 es presenta una implementació pràctica de l'ús de la tecnologia GB per fer millora vegetal de mode precís. La transformació estable en tomaca d'una construcció intragènica que comprén un marcador de selecció intragènic i un regulador de la biosíntesi de flavonoïdes resultà en plantes de tomaca amb un major contingut de flavonols en llur fruits. En conjunt, esta Tesi mostra la implementació de dissenys genètics cada vegada més complexos i precisos en plantes utilitzant elements estàndards i eines modulars seguint els principis de la Biologia Sintètica.
Vázquez Vilar, M. (2016). DESIGN OF GENETIC ELEMENTS AND SOFTWARE TOOLS FOR PLANT SYNTHETIC BIOLOGY [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/68483
TESIS
Premiado
Prescott, Thomas Paul. "Large-scale layered systems and synthetic biology : model reduction and decomposition." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:205a18fb-b21f-4148-ba7d-3238f4b1f25b.
Повний текст джерелаRegårdh, Pernilla C. (Pernilla Christina). "Safe, secure and ethical? : assessing and regulating risks associated with synthetic biology." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/65509.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references (p. 116-127).
Synthetic biology is an emerging field, with a rapidly developing academic-industrial base and the promise of extensive product launches over the next few years. An intense debate over the risks and benefits of synthetic biology has developed even before commercialization. Nongovernmental organizations and official commissions have published over a dozen reports on the potential pitfalls and promise of synthetic biology, with widely varying analytic assumptions, assessment methods, definitions of values, and policy recommendations. How should governments go about developing regulatory policies to govern synthetic biology? This thesis begins by outlining the synthetic biology academic-industrial base, and then describes and critiques official and unofficial assessments of synthetic biology risks and the regulatory policies now in place to regulate risks. It differentiates among risks to security, safety and environment, and ethics, and finds that regulations in each of these areas suffer from significant deficits. Regulations are not well grounded on technical understanding of synthetic biology, lack methodologies for risk assessment of organisms without close natural counterparts, frame risk assessment as a technocratic process without substantial input from stakeholders, and emphasize physical risks to safety and security over non-physical threats to ethics and values. The thesis suggests that the US government and European Union modify existing regulations governing risks associated with synthetic biology and, more fundamentally, processes for developing such regulations to mitigate some of the deficits identified above.
by Pernilla C. Regårdh.
S.M.in Technology and Policy
Camsund, Daniel. "Engineering Transcriptional Systems for Cyanobacterial Biotechnology." Doctoral thesis, Uppsala universitet, Molekylär biomimetik, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-223599.
Повний текст джерелаBrinton, John David. "EVALUATION OF VIBRIO NATRIEGENS AS A SUITABLE METABOLIC ENGINEERING PLATFORM FOR HIGH-VALUE CHEMICAL PRODUCTION." Miami University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=miami1564668650786917.
Повний текст джерелаZhou, Rui. "FITSelect: An Invention to Select Microbial Strains Maximizing Product Formation from a Single Culture Without High-Throughput Screening." Thesis, Virginia Tech, 2011. http://hdl.handle.net/10919/76843.
Повний текст джерелаMaster of Science
Shetty, Reshma P., and Thomas F. Jr Knight. "Engineering transcription-based digital logic devices." Sixth International Conference on Systems Biology, 2005. http://hdl.handle.net/1721.1/29801.
Повний текст джерелаPoster presented at the 2005 ICSB meeting, held at Harvard Medical School in Boston, MA.
Blades, Gareth. "Re-engineering bacterial two-component signalling systems." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:2865c02d-c208-45fa-8108-d8ced9486c19.
Повний текст джерелаMcNamara, Julie H. (Julie Hutton). "Bridging gaps in synthetic biology oversight : iGEM as a testbed for proactive, adaptive risk management." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/90057.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references (pages 84-90).
On the surface, the emerging field of synthetic biology looks highly similar to that of genetic engineering. However, the two fields are based upon divergent underlying logic structures. Whereas genetic engineering affects change through localized modifications of existing organisms, synthetic biology attempts to fuse independent component parts to create wholly novel applications. While legacy regulatory systems were adequate for monitoring biosafety in the early days of the emerging field, as synthetic biology advances, the fundamental differences in its logic structure are creating fissures in the oversight system. A continued reliance on increasingly incompatible mechanisms squanders the limited present opportunity for proactive risk management, and generates increasing potential for significant future risk exposure in the field. This thesis will describe the current state of domestic and international oversight systems relevant to synthetic biology, and characterize their limits and vulnerabilities. It will argue that the current approach of relying on prescriptive, sequence-based controls creates growing gaps in oversight for a field moving toward amalgam organisms, and that the soft methods intended to bridge these gaps, predominantly in the form of institutional biosafety committees, are instead points of additional significant vulnerability. This thesis will also illustrate the challenges that have arisen because of these gaps, both in theory and in practice, through an examination of the International Genetically Engineered Machine competition (iGEM). iGEM, a university-level synthetic biology contest, first served as a valuable case study for illuminating challenges associated with the current system. Later, the Massachusetts Institute of Technology's Program on Emerging Technologies collaborated with iGEM to establish the competition as a policy testbed for demonstrating innovative approaches to biosafety oversight. This thesis will conclude by proposing recommendations for improving biosafety oversight based on lessons learned from the iGEM testbed. First, it is not enough for scientists to recognize that risks exist in their field; as the first line of defense in risk management, they must also be able to identify, understand, and engage with the risks inherent in their own work. Second, in light of the limits imposed on policy revisions due to political gridlock, it is necessary to understand what can be realistically accomplished within the existing federal system, and what instead needs to be achieved outside it. Here, a fuller, more invigorated approach to engagement support is coupled with a mix of improved, adaptive interpretations of the existing oversight system.
by Julie H. McNamara.
S.M. in Technology and Policy
Yeddanapudi, Neelima 1976. "Strategies for designing, testing and demonstrating safety : what synthetic biology can learn from retrospective cases." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/59692.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references (p. 99-101).
Synthetic biology is an emerging technology field within the realm of genetic engineering, differing from traditional genetic engineering in that it focuses on the modularization of genetic parts and the creation of de novo organisms. Significant concerns over safety have been expressed. This research explores traditional engineering and biotechnology practices for overarching principles of design, testing and demonstration that address safety concerns. The information is used to assess the current state of design, testing and demonstration in current synthetic biology projects addressing safety. Component and system design literature provide an engineering backbone of safety systems however, biological attributes such as mutation, growth, and multiplication create safety gaps, where biological engineering practices are needed. These principles are organized into categories of design and testing, and testing and demonstration to gain greater insight on where gaps in the literature might lie. Retrospective cases of traditional engineering and current cases of biotechnologies provide external validation and further illustrate which practices address which design, testing and demonstration needs. While most of the traditional engineering cases addressed safety through design and testing, when they were faced with questions of safety, they presented specific efforts to gain public confidence. The pro-biotics case was different in that the safety concerns came from the scientific community since history is being used as the convincing demonstration of safety. The three synthetic biology research projects cross the divide between traditional engineering and biotechnologies, but theses efforts are firmly in the area of design and testing. These efforts begin to show the tradeoff between implementing safety and faster technical results. Strategies for further research are explored.
by Neelima Yeddanapudi.
S.M.in Technology and Policy
Lightfoot, Shlomiya. "Uncertainty in synthetic biology for release and possibilities for regulation under the Toxic Substances Control Act." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/88400.
Повний текст джерела260
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 52-64).
The emerging field of synthetic biology is developing rapidly and promises diverse applications. Many anticipated applications, particularly those involving release of engineered microbes into the environment or human bodies, have potential environmental and health implications. These implications, which present design challenges to engineers, stem from organisms' potential for competitiveness with natural strains upon entering an environment, their tendency to evolve new characteristics after leaving the lab, and their propensity to exchange genetic material with other organisms they encounter. The field's rapid evolution and the substantial uncertainties in the technology and relevant sciences present challenges to regulators seeking to ensure health and environmental wellbeing. Regulations exhibiting planned adaptation are especially suited to such contexts of uncertainty. However, the synthetic biology applications first nearing commercialization are regulated by the EPA under the Toxic Substances Control Act (TSCA), which was not written to be adaptive. EPA regulators appear to be using TSCA adaptively even though it was not written this way. An examination of characteristics of planned adaptation using the EPA program for ambient air standards as a case study suggests more that the regulators may be able to do to regulate synthetic biology effectively by using TSCA adaptively. Due to statutory language and court history, TSCA is essentially incapable of imposing restrictions or setting standards. Examination of the emerging algal biofuels industry as a case study suggests that concepts of industry-favored regulation may be useful to the EPA for fashioning strong regulations that would promote real health and environmental wellbeing.
by Shlomiya Lightfoot.
S.M. in Technology and Policy
Harris, Andreas William Kisling. "The design of gene regulatory networks with feedback and small non-coding RNA." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:e3a323b1-9067-415d-8728-6c70c1b6cf23.
Повний текст джерелаPozo, Fernández Carlos. "Global optimization applied to kinetic models of metabolic networks." Doctoral thesis, Universitat Rovira i Virgili, 2012. http://hdl.handle.net/10803/96660.
Повний текст джерелаIn recent years, the use of genetic manipulation techniques has opened the door for obtaining microorganisms with enhanced phenotypes, which has in turn led to significant improvements in the synthesis of certain biochemical products. However, mutation and selection of these new organisms has been performed, in most cases, in a trial-and-error basis. It is expected that these processes could be further improved if quantitative design principles were used to guide the search towards the ideal enzymatic profiles. This thesis is devoted to developing a set of advanced global optimization tools to assess metabolic engineering problems and other questions arising in systems biology. In particular, we focus on problems where metabolic networks are modeled making use of kinetic expressions. The usefulness of the algorithms developed to solve such problems is demonstrated by means of several case studies.
Boada, Acosta Yadira Fernanda. "A systems engineering approach to model, tune and test synthetic gene circuits." Doctoral thesis, Universitat Politècnica de València, 2018. http://hdl.handle.net/10251/112725.
Повний текст джерелаLa biologia sintètica es defineix com l'enginyeria de la biologia: el (re) disseny i construcció de noves parts, dispositius i sistemes biològics per a realitzar noves funcions útils que es basen a principis elucidats de la biologia i l'enginyeria. Per facilitar la construcció ràpida, reproduïble i predictible de aquests sistemes biològics a partir de conjunts de components és necessari desenvolupar nous mètodes i eines. La tesi planteja la optimització multiobjectiu com el marc adequat per a tractar els problemes comuns que apareixen en el disseny racional i l' ajust òptim dels circuits genètics sintètics. Utilitzant un enfocament clàssic d'enginyeria de sistemes, la tesi es centra principalment en: i) el modelatge de circuits genètics sintètics basat en primers principis, ii) l' estimació de paràmetres de models a partir de dades experimentals i iii) l' ajust basat en models per aconseguir el rendiment desitjat dels circuits. S'han utilitzat dos circuits genètics sintètics de diferent naturalesa i amb diferents objectius i problemes: un circuit de prealimentació de tipus 1 incoherent (I1-FFL) que exhibeix la important propietat biològica d'adaptació, i un circuit de quorum sensing i realimentació (QS/Fb) que comprèn dos bucles de realimentació entrellaçats -un intracel·lular i un basat en la comunicació de cèl·lula a cèl·lula- dis-senyat per regular el nivell mitjà d'expressió normal d'una proteïna d'interès mentre es minimitza la seua variació al llarg de la població de cèl·lules. Els dos circuits han estat analitzats in silico i implementats in vivo. En tots dos casos, s'han desenvolupat models basats en primers principis d'aquests circuits. Després es presta especial atenció a delinear com obtenir models d'ordre reduït susceptibles de estimació de paràmetres, però mantenint el significat biològic. L' estimació dels paràmetres del model a partir de les dades experimentals es considera en diferents escenaris, tant utilitzant models determinístics com estocàstics. Per al circuit I1-FFL es consideren models determinístics. La tesi planteja la utilització de models locals utilitzant la optimització multiobjectiu per realitzar l'estimació de parametres del model sota escenaris amb estructura de model incompleta (dinàmica no modelada). Per al circuit de QS/Fb, una estructura controlada per realimentació, el problema tractat és la manca d'excitabilitat dels senyals. La tesi proposa una metodologia de estimació en dues etapes utilitzant models estocàstics. La metodologia permet utilitzar dades de curs temporal promediats de la població i mesures de distribució en estat estacionari d'una sola una cèl·lula. L' ajust de circuits basat en models per aconseguir el rendiment desitjat dels circuits també s' aborda mitjançant la optimització multiobjectiu. Per al circuit QS/Fb, es fa un anàlisi estocàstic complet. La tesi aborda com tenir en compte correctament tant el soroll intrínsec com l' extrínsec, les dues principals fonts de soroll en els circuits genètics sintètics. S' analitza l'equilibri entre dues fonts de soroll i el paper que exerceixen en el bucle de realimentació intracel·lular, les i en la realimentació extracel·lular de tota la població. La principal conclusió es que la complexa interacció entre els dos canals de realimentació fa necessari l' ús de la optimització multiobjectiu per al adequat ajust del circuit. En aquesta tesi, a més de l'ús adequat d'eines d'optimització multiobjectiu, la principal preocupació és com derivar directives per al ajust in silico de paràmetres de circuits que puguin aplicar-se de forma realista en viu en un laboratori estàndard. Així, com a alternativa a l'anàlisi de sensibilitat de paràmetres clàssic, la tesi proposa l'ús de l' tècniques de l'agrupació al llarg dels fronts de Pareto, relacionant el compromís de dessempeny amb les regions en l'espai d'paràmetres.
Synthetic biology is defined as the engineering of biology: the deliberate (re)design and construction of novel biological and biologically based parts, devices and systems to perform new functions for useful purposes, that draws on principles elucidated from biology and engineering. Methods and tools are needed to facilitate fast, reproducible and predictable construction of biological systems from sets of biological components. This thesis raises multi-objective optimization as the proper framework to deal with common problems arising in rational design and optimal tuning of synthetic gene circuits. Using a classical systems engineering approach, the thesis mainly addresses: i) synthetic gene circuit modeling based on first principles, ii) model parameters estimation from experimental data and iii) model-based tuning to achieve desired circuit performance. Two gene synthetic circuits of different nature and with different goals and inherent problems have been used throughout the thesis: an Incoherent type 1 feedforward circuit (I1-FFL) that exhibits the important biological property of adaptation, and a Quorum sensing/Feedback circuit (QS/Fb) comprising two intertwined feedback loops -an intracellular one and a cell-to-cell communication-based one-- designed to regulate the mean expression level of a protein of interest while minimizing its variance across the population of cells. Both circuits have been analyzed in silico and implemented in vivo. In both cases, circuit modeling based on first principles has been carried out. Then, special attention is paid to illustrate how to obtain reduced order models amenable for parameters estimation yet keeping biological significance. Model parameters estimation from experimental data is considered in different scenarios, both using deterministic and stochastic models. For the I1-FFL circuit, deterministic models are considered. In this case, the thesis raises ensemble modeling using multi-objective optimization to perform model parameters estimation under scenarios with incomplete model structure (unmodeled dynamics). For the QS/Fb gene circuit, a feedback controlled structure, the lack of excitability of the signals is the problem addressed. The thesis proposes a two-stage estimation methodology using stochastic models. The methodology allows using population averaged time-course data and steady state distribution measurements at the single-cell level. Model-based circuit tuning to achieve desired circuit performance is also addressed using multi-objective optimization. First, for the QS/Fb feedback control circuit, a complete stochastic analysis is performed. Here, the thesis addresses how to correctly take into account both intrinsic and extrinsic noise, the two main sources of noise in gene synthetic circuits. The trade-off between both sources of noise, and the role played by in the intracellular single-cell feedback loop and the extracellular population-wide feedback is analyzed. The main conclusion being that the complex interplay between both feedback channels compel the use of multi-objective optimization for proper tuning of the circuit to achieve desired performance. Thus, the thesis wraps up all the previous results and uses them to address circuit tuning for desired performance. Here, besides the proper use of multi-objective optimization tools, the main concern is how to derive guidelines for circuit parameters tuning in silico that can realistically be applied in vivo in a standard laboratory. Thus, as an alternative to classical parameters sensitivity analysis, the thesis proposes the use of clustering techniques along the optimal Pareto fronts relating the performance trade-offs with regions in the circuits parameters space.
This work has been partially supported by the Spanish Government (CICYT DPI2014- 55276-C5-1) and the European Union (FEDER). The author was recipient of the grant Formación de Personal Investigador by the Universitat Politècnica de València, subprogram 1 (FPI/2013-3242). She was also recipient of the competitive grants for pre-doctoral stays Erasmus Student Placement-European Programme 2015, and FPI Mobility program 2016 of the Universitat Politècnica de València. She also received the competitive grant for a pre-doctoral stay Becas de movilidad para Jóvenes Profesores e Investigadores 2016, Programa de Becas Iberoamérica of the Santander Bank.
Boada Acosta, YF. (2018). A systems engineering approach to model, tune and test synthetic gene circuits [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/112725
TESIS
Rocha, Andrea M. "Computational Discovery of Phenotype Related Biochemical Processes for Engineering." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3315.
Повний текст джерелаStimple, Samuel Douglas. "Recent Advances in Developing Molecular Biotechnology Tools for Metabolic Engineering and Recombinant Protein Purification." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1514494485801145.
Повний текст джерелаMoreno, de Palma Isabel. "Metabolic channeling for biofuel production : Co-localization of Pdc and Adh." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-319519.
Повний текст джерелаBellancini, Michele. "Engineering the synthesis of lantibiotics in e. Coli by combining the cynnamicin and nisin modification systems." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amslaurea.unibo.it/8625/.
Повний текст джерелаNOBILE, MARCO SALVATORE. "Evolutionary Inference of Biological Systems Accelerated on Graphics Processing Units." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2015. http://hdl.handle.net/10281/75434.
Повний текст джерелаAdotey, Bless. "MATHEMATICAL MODELING OF CLOSTRIDIUM THERMOCELLUM’S METABOLIC RESPONSES TO ENVIRONMENTAL PERTURBATION." UKnowledge, 2011. http://uknowledge.uky.edu/bae_etds/1.
Повний текст джерелаCourbet, Alexis. "Engineering autonomous and programmable biosensors through synthetic biology : integrating multiplexed biomarker detection and biomolecular signal processing into next-generation diagnostics." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONT3513.
Повний текст джерелаThe promise for real precision medicine is contingent on novel technological solutions to diagnosis. In the post-genomic era, synthetic biology approaches to medicine provide new ways to probe, monitor and interface human pathophysiology. Emerging as a mature field increasingly transitioning to the clinics, synthetic biology can be used to apply engineering principles to design and build biological systems with clinical specifications. A particularly tantalizing application is to develop versatile, programmable and intelligent diagnostic devices closely interconnected with therapy. This thesis presents novel engineering concepts and approaches to design synthetic biological devices interfacing human diseases in clinical samples through biomolecular digital signal processing, in light of a need for dramatic improvements in capabilities and robustness. It addresses primarily the engineering of synthetic gene circuits through integrase based digital genetic amplifiers and logic gates, to integrate modular and programmable biosensing of biomarkers and diagnostic decision algorithms into bacteria. It then investigates systematic bottom-up methodologies to program microscale synthetic protocells performing medical biosensing and biocomputing operations. We demonstrate streamlined microfluidic fabrication methods and solutions to implement complex Boolean operation using integrated synthetic biochemical circuits. This contribution also extends to the characterization of protocell design space through novel computer assisted design frameworks, as well as the analysis of mathematical and biological evidence for universal protocellular biocomputing devices. The articulation of biological governing principles and medical implications for the synthetic devices developed in this work was further validated in the clinic, and initiates new models towards next-generation diagnostics. This work envisions that synthetic biology is preparing the future of medicine, supporting and speeding up the development of diagnostics with novel capabilities to bring direct improvement in biotechnologies from the clinical lab to the patient
Vidiella, Rocamora Blai 1993. "Terraforming Earth's ecosystems : engineering ecosystems to avoid anthropogenic tipping points." Doctoral thesis, TDX (Tesis Doctorals en Xarxa), 2022. http://hdl.handle.net/10803/673774.
Повний текст джерелаViberg, Victor. "Quantifying metabolic fluxes using mathematical modeling." Thesis, Linköpings universitet, Institutionen för medicinsk teknik, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-149588.
Повний текст джерелаDuportet, Xavier. "Developing new tools and platforms for mammalian synthetic biology : From the assembly and chromosomal integration of complex dna circuits to the engineering of artificial intercellular communication systems." Paris 7, 2014. http://www.theses.fr/2014PA077262.
Повний текст джерелаMammalian synthetic biology may provide novel therapeutic strategies, help decipher new paths for drug discovery and facilitate synthesis of valuable molecules. Yet, our capacity to program cells is currently hampered both by the lack of efficient approaches to streamline the design, construction and screening of synthetic gene networks, and also by the complexity of mammalian systems and our poor understanding of cellular processes context¬dependencies. To address these problems, I proposed and validated a number of concepts and approaches during my PhD. First, I created a framework for modular and combinatorial assembly of functional (multi)gene expression vectors and their efficient and specific targeted integration into a well-defined chromosomal context in mammalian cells. Second, I developed a platform to identify and characterize new serine reconnbinase systems from Mycobacteriophage genomes in order to extend the toolbox of genome engineering techniques available for mammalian cells progranning. To overcome the apparent limitations in our single-tell rational engineering capacity, I also engineered two new artificial intercellular communication systems for mammalian cells, in order to facilitate the spatial decoupling of different modules of a synthetic circuit. Even though we are still years away from therapies using engineered cells carrying synthetic circuits to repair damaged or non-functional organs or to create de-novo tissues, I believe the contributions developed during the course of my PhD could potentially be used to help fasten the development of therapeutically relevant DNA circuits or to provide new means to understand mechanisms of cellular processes.
Arense, Parra Paula. "Estrategias de ingeniería metabólica y biología de sistemas aplicadas a la producción de L(-)carnitina por Escherichia coli= Metabolic engineering and systems biology strategies for L(-)carnitine production in Escherichia coli." Doctoral thesis, Universidad de Murcia, 2014. http://hdl.handle.net/10803/146175.
Повний текст джерелаTwo parallel research aims addressed on Escherichia coli are shown in this PhD thesis. On one hand, the optimization of a biotransformation process in order to improve L( )-carnitine synthesis by using metabolic engineering techniques is explained within the first chapters. On the other hand, in the following chapters, the main effects provoked by long-term high salt concentrations and the adaptative response to osmotic stress were determined using different techniques related to systems biology. L( )-carnitine is an important trimethylammonium compound because of its role in the energetic metabolism, in humans, several pathologies are related with deficiencies of carnitine level. Several works focused on the therapeutic application of L( )-carnitine, showed that administration of this compound could be a solution as opposed to its absence. Once different carnitine production ways were revised, this work shows an alternative method using Escherichia coli to carry out the biotransformation from D(+)-carnitine and/or crotonobetaine into L( )-carnitine. By using molecular biology techniques a strain of E. coli was engineered, obtaining caiC overexpression and enhancing the production yield respect to the wild type strain. Moreover, several aspects related with carnitine metabolism, such as coenzyme A availability and the inhibition of specific metabolic pathways were studied to optimize the carnitine production. Afterwards, various metabolic engineering strategies were implemented, obtaining a stable engineered strain with high capacity to produce L( )-carnitine. The modifications carried out were: a) deletion of the aceK gene (encoding a bifunctional protein phosphatase/kinase which performs post-translational control of isocitrate dehydrogenase) in order to increase the metabolic flux towards TCA cycle, b) deletion of the caiA gene (encoding the crotonobetainyl-CoA reductase) to avoid synthesis of γ-butyrobetaine (byproduct of the carnitine metabolism), and c) replacement of the highly regulated natural promoter of the cai operon by a constitutive promoter. These mutations implemented in the same strain led to obtaining almost 100% conversion from crotonobetaine to L( )-carnitine in the assay conditions. Moreover, the main restrictions impossed to the aerobic expression of the carnitine metabolism were eliminated producing L( ) carnitine in the presence of oxygen. Therefore, this work emphasizes the important role of metabolic engineering to improve any biotechnological process. On the other hand, L( )-carnitine and similar compounds are used as osmoprotectors, which are accumulated in high concentrations, either through the uptake from the medium or through de novo synthesis inside the cells, to avoid dehydratation when the osmolarity of the culture medium increases. Under these conditions, microorganisms have different response to an environmental stress, short-term or shock and long-term adaptation. In this work, evolution and response to long-term adaptation were analyzed in a E. coli strain growing in continuous reactors supplemented with a gradually increasing concentration of NaCl (moderate, high and very high). Enzyme activities from the main metabolic pathways and fermentative metabolites were analyzed, highlighting important role of central metabolism on adaptation and cellular survival after salt stress exposition. Furthermore, the need of biosynthetic precursors and energy as ATP were shown. In addition, a systems biology approach was conducted to study cellular behavior. In order to estimate the critical modifications undergone to overcome stress and to develop tolerance to salt, the metabolism was examined at several levels using different techniques (metabolomics, fluxomics and transcriptomics). Under salt stress conditions two set of responses were shown. One of them was focused to maintain the energetic threshold in cells, thus, either an increment of the metabolic pathways which could produce energy or a decrease of no-essential processes to survive were shown. On the other hand, cells under high or very high salt concentrations showed another similar response characterized by both changing on pattern of fermentative pathways and redox state. Therefore, using suitable techniques many changes in the physiology and metabolism of the E. coli strain in use were detected. Moreover, the systems biology approach offered a way to obtain and integrate a large amount of information, preventing some of the information being overlooked by the massive amount of data. Both the metabolic engineering and systems biology approaches have provided excellent ways to improve and know features of microorganisms involved in biotechnological processes related with the L( )-carnitine production.
Montagud, Aquino Arnau. "Modelling and analysis of biological systems to obtain biofuels." Doctoral thesis, Universitat Politècnica de València, 2012. http://hdl.handle.net/10251/17319.
Повний текст джерелаThis thesis is focused on the construction and uses of genome-scale metabolic models to efficiently obtain biofuels, such as ethanol and hydrogen. As a target organism, cyanobacterium Synechocystis sp. PCC6803 was chosen. This organism has been studied as a potential photon-fuelled production platform, for its ability to grow only from carbon dioxide, water and photons. This dissertation verses about methods to model, analyse, estimate and predict the metabolic behaviour of cells. Principal goal is to extract knowledge from the different biological aspects of an organism in order to use it for an industrial relevant objective. This dissertation has been structured in chapters accordingly organized as the successive tasks that end up building an in silico cell that behaves as the carbon-based one. This process usually starts with the genome annotation files and ends up with a genome-scale metabolic model able to integrate ¿omics data. First objective of present thesis is to reconstruct a model of this cyanobacteria¿s metabolism that accounts for all the reactions present in it. This reconstruction had to be flexible enough as to allow growth under the different environmental conditions under which this organism grows in nature as well as to allow the integration of different levels of biological information. Once this requisite was met, environmental variations could be simulated and their effect studied under a system-wide perspective. Up to five different growth conditions were simulated on this metabolic model and differences were evaluated. Following assignment was to define production strategies to weigh this organism¿s viability as a production platform. Genetic perturbations were simulated to design strains with an enhanced production of three industrially-relevant metabolites: succinate, ethanol and hydrogen. Resulting sets of genetic modifications for the overproduction of those metabolites are, thus, proposed. Moreover, functional reactions couplings were studied and weighted to their metabolite production importance. Finally, genome-scale metabolic models allow establishing integrative approaches to include different types of data that help to find regulatory hotspots that can be targets of genetic modification. Such regulatory hubs were identified upon light/dark shifts and general metabolism operational principles inferred. All along this process, blind spots in Synechocystis sp. PCC6803 metabolism, and more importantly, blind spots in our understanding of it, are revealed. Overall, the work presented in this thesis unveils the industrial capabilities of cyanobacterium Synechocystis sp. PCC6803 to evolve interesting metabolites as a clean production platform.
Esta tesis es centra en la construcció i els usos del models metabòlics a escala genòmica per a obtenir eficientment biocombustibles, com etanol i hidrogen. Com a organisme diana, s¿elegí el cianobacteri Synechocystis sp. PCC6803. Aquest organisme ha segut estudiat com una plataforma de producció nodrida per fotons, per la seva habilitat per créixer a partir únicament de diòxid de carboni, aigua i fotons. Aquesta tesi versa sobre mètodes per a modelitzar, analitzar, estimar i predir el comportament metabòlic de cèl¿lules. La principal meta és extreure coneixement del diferents aspectes biològics d¿un organisme de manera que s¿usen per a un objectiu industrial rellevant. La tesi ha segut estructurada en capítols organitzats d¿acord a les successives tasques que acaben construint una cèl¿lula in silico que es comporta, idealment, com la que està basada en carboni. Aquest procés generalment comença amb els arxius de l¿anotació del genoma i acaba amb un model metabòlic a escala genòmica capaç d¿integrar dades ¿òmiques. El primer objectiu de la present tesi és la reconstrucció d¿un model del metabolisme d¿aquest cianobacteri que tinga en compte totes les reaccions que hi estan presents. Esta reconstrucció havia de ser prou flexible com per permetre la simulació del creixement en les diferents condicions ambientals en les quals aquest cianobacteri creix en la natura, així com permetre la integració de diferents nivells d¿informació biològica. Una vegada que aquest requisit fou assolit, es pogueren simular variacions ambientals i estudiar els seus efectes amb una perspectiva de sistema. S¿han simulat fins a cinc condicions de creixement en este model metabòlic i les seves diferències han segut avaluades. La següent tasca fou definir estratègies de producció per a valorar la viabilitat d¿aquest organisme com a plataforma de producció. Es simularen pertorbacions genètiques per al disseny de soques amb producció millorada de metabòlits de rellevància industrial: succinat, etanol i hidrogen. Així, es proposen conjunts de modificacions genètiques per a la sobreproducció d¿aquests metabòlits. També s'han estudiat reaccions acoblades funcionalment i s¿ha ponderat la seva importància en la producció de metabòlits. Finalment, els models metabòlics a escala genòmica permeten establir criteris per integrar diferents tipus de dades que ens ajuden a trobar punts importants de regulació. Eixos centres reguladors, que poden ser objecte de modificacions genètiques, han segut investigats baix canvis dràstics d¿il¿luminació i s¿han inferit principis operacionals del metabolisme. Al llarg d'aquest procés, s¿han revelat punts cecs al metabolisme de Synechocystis sp. PCC6803 i, el més important, punts cecs en la nostra comprensió d'aquest metabolisme. En general, el treball presentat en aquesta tesi dona a conèixer les capacitats industrials del cianobacteri Synechocystis sp. PCC6803 per a produir metabòlits d'interès, tot sent una plataforma de producció neta i sostenible.
Montagud Aquino, A. (2012). Modelling and analysis of biological systems to obtain biofuels [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/17319
Palancia
Park, Young kyoung. "Metabolic engineering of the yeast Yarrowia lipolytica for the production of even- and odd-chain fatty acids." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASB010.
Повний текст джерелаMicrobial oils are regarded as promising alternatives to fossil fuels with growing environmental and energy concerns. Odd-chain fatty acids (OCFAs), a type of unusual lipids, are value-added compounds with various biotechnological applications. The objective of the thesis was to develop Yarrowia lipolytica as a platform strain for the production of OCFAs by metabolic engineering.For developing Y. lipolytica, the identification and characterization of a new series of erythritol-hybrid-inducible promoters (pEYK1, pEYD1, and derivatives) were explored. The hybrid promoter series showed variable strengths, erythritol-based induction increased 2.2 to 32.3 times in the WT strain and 2.9 to 896.1 times in the eyk1Δ strain, which will improve the modulation of gene expression for metabolic engineering of Y. lipolytica.For OCFA production, tolerance to propionate was studied. Two genes, RTS1 and MFS1, were identified as propionate-tolerant genes by screening a genomic DNA library. Through metabolic engineering strategies, such as inhibiting competitive pathways, increasing precursor pools, and enhancement of total lipid accumulation, OCFA production was increased from 0.14 g/L to 1.87 g/L. De novo production of OCFAs without propionate supplementation was also explored by overexpression of the threonine synthesis pathway. OCFAs production was increased by 12-times; 0.36 versus 0.03 g/L for WT.In summary, Y. lipolytica strains were developed to produce high-amount of OCFAs, mainly heptadecenoic acid. This work paves the way for the microbial production of OCFAs and their derivatives at the industrial scale
Boehm, Christian Reiner. "Gene expression control for synthetic patterning of bacterial populations and plants." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/267842.
Повний текст джерелаSarrade-Loucheur, Arthur. "Biosynthèse de nouveaux dérivés de l'alpha-bisabolol par une approche de biologie synthèse." Thesis, Toulouse, INSA, 2020. http://www.theses.fr/2020ISAT0003.
Повний текст джерелаThe rise of synthetic biology now enables the production of new to nature molecules. In the frame of this thesis we focused on the diversification of the (+)-epi-α-bisabolol scaffold. This molecule coming from the plant Lippia dulcis belongs to the vast family of sesquiterpenes. While sesquiterpenes possess diverse biological activities, (+)-epi-α-bisabolol is the precursor of hernandulcin, an intense sweetener. However, the last oxidative step(s) of the hernandulcin biosynthetic pathway remain elusive.Rather than seeking the native oxidase responsible for hernandulcin synthesis among L. dulcis enzymes we selected oxidative enzymes known to be promiscuous and that could functionalize (+)-epi-α-bisabolol in order to i) generate diversity from (+)-epi-α-bisabolol; ii) hopefully identify an oxidative enzyme catalyzing hernandulcin synthesis. First, a yeast chassis strain enabling the in vivo screening of cytochromes P450 (CYPs) was constructed by coexpressing two key enzymes: the (+)-epi-α-bisabolol synthase (BBS) and the NADPH cytochrome P450 reductase. Then, the in vivo screening assays revealed that 5 CYPs out of our library of 25 animal CYPs involved in xenobiotic metabolism oxidized (+)-epi-α-bisabolol and produced new hydroxylated regioisomers. Of the oxidized products, the structure of one compound, 14-hydroxy-(+)-epi-α-bisabolol, was fully elucidated by NMR while the probable structure of a second one was determined (9-hydroxy-(+)-epi-α-bisabolol). In parallel, the production of (+)-epi-α-bisabolol derivatives was enhanced through addition of a supplementary genomic copy of BBS that augmented the final titer of hydroxylated product to 64 mg/L. We thus demonstrate that promiscuous drug metabolism CYPs can be used to produce novel compounds from a sesquiterpene scaffold.Furthermore, different products were obtained with two homologous enzymes i.e. CYP2B6 and CYP2B11. This prompted us to study the molecular determinants putatively responsible for enzyme regiospecificity. From chimeric enzymes composed of secondary structure elements originating from CYP2B6 and CYP2B11 we were not able to identify specific motifs that could explain the CYPs regiospecificity. This approach suggests that the molecular determinants cannot be attributed to specific structural elements of the two enzymes but are rather widespread in the protein sequences.In order to generate a wider molecular diversity from α-bisabolol or hernandulcin, and synthesize molecules with different physico-chemical and biological properties (i.e. solubility, sweetening power etc.), we attempted the glycosylation of these compounds using a plant glucosyltransferase (UGT93B16) or human glucuronosyltransferases. UGT93B16 was found to glucosylate both (-)-α-bisabolol and hernandulcin. In addition, we carried out whole cell catalysis using E. coli and S. cerevisiae as recombinant producers of UGT93B16. Comparison of the two microbial hosts showed that glycosylation using yeast cells was more efficient. In parallel, we investigated α-bisabolol glucosylation by human UDP-glucuronosyltransferases involved in the xenobiotic metabolism. In vitro enzymatic assays demonstrated a weak activity of UGT1A9, UGT2B4 and UGT2B7 towards α-bisabolol and hernandulcin. However, their introduction in yeast failed to produce detectable amounts of glucuronide products. In summary, we proved the feasibility of producing new to nature sesquiterpene glucosides using either enzyme-based assay or bioconversion in two different hosts that are widely used in biotechnology.To conclude, the approaches used in this thesis highlight the assets of screening promiscuous enzymes for the production of new molecules from α-bisabolol. We also explored the limits of our chassis strain and a tighter regulation of S. cerevisiae metabolism could improve the production (+)-epi-α-bisabolol oxidized products. Finally, the coupling in yeast of cytochrome P450 and glucosyltransferase steps can now be envisioned
Trebulle, Pauline. "Modélisation multi-échelles de réseaux biologiques pour l’ingénierie métabolique d'un châssis biotechnologique." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLA022/document.
Повний текст джерелаMetabolism defines the set of biochemical reactions within an organism, allowing it to survive and adapt to different environments. Regulating these reactions requires complex processes involving many effectors interacting together at different scales.Developing models of these regulatory networks is therefore an essential step in better understanding the precise mechanisms governing living systems and ultimately enabling the design of synthetic, self-regulating and adaptive systems at the genome level. As part of this interdisciplinary work, we propose to use an iterative network inference and interrogation approach to guide the engineering of the metabolism of the yeast of industrial interest Yarrowia lipolytica.Based on transcriptomic data, the first network for the regulation of adaptation to nitrogen limitation and lipid production in this yeast was inferred.The interrogation of this network has then allowed to to highlight and experimentally validate the impact of several regulators on lipid accumulation. In order to further explore the relationships between regulation and metabolism, a new method, CoRegFlux, has been proposed for the prediction of metabolic phenotype based on the influence profiles of regulators in the studied conditions. This R package, available on the Bioconductor platform, was then used to better understand adaptation to nitrogen limitation and to identify phenotypes of interest for strain engineering, particularly for the production of lipids and amino acid derivatives such as violacein.Thus, through an iterative approach, this work provides new insights into the interactions between regulation and metabolism in Y. lipolytica, conserved regulatory module in this yeast and contributes to the development of innovative integrative methods for computer-assisted strain design
Bicen, Ahmet Ozan. "Fundamentals of molecular communication over microfluidic channels." Diss., Georgia Institute of Technology, 2016. http://hdl.handle.net/1853/55009.
Повний текст джерелаGoelzer, Anne. "Emergence de structures modulaires dans les régulations des systèmes biologiques : théorie et applications à Bacillus subtilis." Phd thesis, Ecole Centrale de Lyon, 2010. http://tel.archives-ouvertes.fr/tel-00597796.
Повний текст джерелаWang, Tiebin. "Fitness costs in antibiotic resistance and metabolic engineering." Thesis, 2020. https://hdl.handle.net/2144/41693.
Повний текст джерела"Biosynthetic Production of Aromatic Fine Chemicals." Doctoral diss., 2016. http://hdl.handle.net/2286/R.I.38586.
Повний текст джерелаDissertation/Thesis
Doctoral Dissertation Chemical Engineering 2016