Mammalian synthetic biology: Engineering of sophisticated gene networks

Greber, David; Fussenegger, Martin

doi:10.1016/j.jbiotec.2007.05.014

Cited by 88 publications

(53 citation statements)

References 96 publications

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“…Out of several different variants, a promoter with seven lux boxes worked the best and is thus called pLuxO7. A variety of lux signal transducers were also designed and tested [47][48][49]. In the presence of 3OC6HSL, LuxRm binds and activates transcription from the mammalian lux promoter pLuxO7.…”

Section: B) Signal Detectionmentioning

confidence: 99%

“…An optimized 'waiting period' can be introduced by synthetic cascades consisting of repressors (i.e. genetic logic inverters) connected in series [49,53,58,59,193,194]. This second stage attack will involve the sentinels bursting (using E-protein discussed in Chapter 2 Section III (a)), and releasing large quantities of a broader spectrum toxin into the medium to kill any remaining pathogen.…”

Section: Bacterial Adaptive Response Systemmentioning

confidence: 99%

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Genetically Programmable Pathogen Sense and Destroy

Gupta¹,

Weiss²

2010

SciVee

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Twenty five percent of all the deaths worldwide are caused by infectious diseases. They are also the biggest cause of mortality among children under five years of age. Among them diarrheal diseases alone cause as many deaths as AIDS or TB and malaria combined. Also up to 80% of traveler's diarrhea is bacterial in nature. Vibrio cholerae (cholera), Salmonella spp (typhoid fever), Shigella spp (shigellosis) and a variety of enteropathogenic Escherichia coli strains are among the principle bacterial agents that cause this type of diarrhea.

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Section: B) Signal Detectionmentioning

confidence: 99%

Section: Bacterial Adaptive Response Systemmentioning

confidence: 99%

Genetically Programmable Pathogen Sense and Destroy

Gupta¹,

Weiss²

2010

SciVee

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“…But this technology is increasingly also applied in human cells [12], which might for example enable novel applications in gene therapy. This development of the technology can raise ethical question, particularly if it is applied in human embryonic stem cells [13].…”

Section: Synthetic Biology In Mammalian Cellsmentioning

confidence: 99%

The Ethics of Synthetic Biology: Outlining the Agenda

2009

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The projects and aims of synthetic biology raise various ethical questions, challenging some of our basic moral concepts. This chapter addresses these issues in three steps. First, we present an overview of different types of ethical issues related to synthetic biology by assigning them to three main categories: method-related, application-related, and distribution-related issues. The first category concerns the procedure and aims of synthetic biology, the second deals with certain planned applications of synthetic biology and the third with questions of distribution and access to procedures and products of this technology. Next, we address a statement often raised in the discussion about ethics of synthetic biology, namely that the ethical issues of synthetic biology have been discussed in previous debates and therefore do not need to be addressed again. We argue that past debates do not render the discussion of ethical issues superfluous because synthetic biology sets these issues in a new context and because the discussion of such issues fulfills in itself an important function, namely by stimulating thought about our relationship to technology and nature. Furthermore, given that synthetic biology's aims go beyond those of previous technologies, we suggest that it does in fact raise novel ethical issues. Finally, we present opinions of European synthetic biologists on ethical issues in their field. At such an early stage of technological development, synthetic biologists play an important role in the assessment of their discipline, and are best placed to estimate the scientific potential of the field. In an attempt to capture the intuitions of the European synthetic biology community, we have carried out interviews, the results of which we briefly summarize in this last section. By presenting an overview of the various ethical issues and their actual and perceived importance, this chapter aims at providing a first outline for the agenda for an ethics of synthetic biology.

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“…This type of research has a long tradition in Systems Biology (Savageau, 1972;1976). The recent field of Synthetic Biology (see Arkin, 2001;Forster and Church, 2007;Greber and Fussenegger, 2007;Luisi, 2007;Meyer et al, 2007;Pleiss, 2006;Saito and Inoue, 2007;Sole et al, 2007 for reviews) heavily depends on the ability to characterize the underlying rules that govern the systemic behavior of a network. These rules are then used to create systems with specific performances.…”

Section: Introduction: Goals Of Mathematical Modelingmentioning

confidence: 99%

“…These rules are then used to create systems with specific performances. As examples of such applications we have the oscillatory clock designed by Ninfa, Savageau and co-workers in E. coli (Atkinson et al, 2003), or the bistable switch designed by Kim et al (2006), among others (Antunes et al, 2006;Atsumi and Little;2006, Fung et al, 2005Greber and Fussenegger, 2007;Haseltine and Arnold, 2007;Kim et al, 2006;Rosenfeld et al, 2007;Sprinzak and Elowitz, 2005;Weber et al, 2007;Yokobayashi et al, 2002). Identifying and analyzing design principles is, perhaps, the application discussed in this review for which mathematical models are more central as a tool .…”

Section: Introduction: Goals Of Mathematical Modelingmentioning

confidence: 99%

Mathematical formalisms based on approximated kinetic representations for modeling genetic and metabolic pathways

Alves

Vilaprinyó

Hernández‐Bermejo

et al. 2008

Biotechnology and Genetic Engineering Reviews

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Citing articles: 16 View citing articles Biotechnology and Genetic Engineering Reviews -Vol. 25, 1-40 (2008) AbstractThere is a renewed interest in obtaining a systemic understanding of metabolism, gene expression and signal transduction processes, driven by the recent research focus on Systems Biology. From a biotechnological point of view, such a systemic understanding of how a biological system is designed to work can facilitate the rational manipulation of specific pathways in different cell types to achieve specific goals. Due to the intrinsic complexity of biological systems, mathematical models are a central tool for understanding and predicting the integrative behavior of those systems. Particularly, models are essential for a rational development of biotechnological applications and in understanding system's design from an evolutionary point of view. Mathematical models can be obtained using many different strategies. In each case, their utility will depend upon the properties of the mathematical representation and on the possibility of obtaining meaningful parameters from available data. In practice, there are several issues at stake when one has to decide which mathematical model is more appropriate for the study of a given problem. First, one needs a model that can represent the aspects of the system one wishes to study. Second, one must choose a mathematical representation that allows an accurate analysis of the system with respect to different aspects of interest (for example, robustness of the system, dynamical behavior, optimization of the system with respect to some production goal, parameter value determination, etc). Third, before choosing between alternative and equally appropriate mathematical representations for the system, one should compare representations with respect to easiness of automation for model set-up, simulation, and analysis of results. Fourth, one should also consider how to facilitate model transference and re-usability by other researchers and for distinct purposes. Finally, one factor that is important for all four aspects is the regularity in the mathematical structure of the equations because it facilitates computational manipulation. This regularity is a mark of kinetic representations based on approximation theory. The use of approximation theory to derive mathematical representations with regular structure for modeling purposes has a long tradition in science. In most applied fields, such as engineering and physics, those approximations are often required to obtain practical solutions to complex problems. In this paper we review some of the more popular mathematical representations that have been derived using approximation theory and are used for modeling in molecular systems biology. We will focus on formalisms that are theoretically supported by the Taylor Theorem. These include the Power-law formalism, the recently proposed (log)linear and Lin-log formalisms as well as some closely related alternatives. We will analyze the similarities and differences between...

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Mammalian synthetic biology: Engineering of sophisticated gene networks

Cited by 88 publications

References 96 publications

Genetically Programmable Pathogen Sense and Destroy

Genetically Programmable Pathogen Sense and Destroy

The Ethics of Synthetic Biology: Outlining the Agenda

Mathematical formalisms based on approximated kinetic representations for modeling genetic and metabolic pathways

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