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Using Network Biology to Bridge Pharmacokinetics and Pharmacodynamics in Oncology

D C Kirouac, M D Onsum
2013 CPT: Pharmacometrics & Systems Pharmacology  
design combination therapies and identify predictive biomarkers in silico.  ...  If mathematical modeling is to be used effectively in cancer drug development, future models must take into account both the mechanistic details of cellular signal transduction networks and the pharmacokinetics  ...  Homeostatic regulation typically involves feedback control circuits, and many biochemical feedback circuits have been characterized.  ... 
doi:10.1038/psp.2013.38 pmid:24005988 pmcid:PMC4026631 fatcat:fc5thni2arclnotehnjxspq5pi

Principles for designing synthetic microbial communities

Nathan I Johns, Tomasz Blazejewski, Antonio LC Gomes, Harris H Wang
2016 Current Opinion in Microbiology  
Advances in synthetic biology to build microbes with defined and 20 controllable properties are enabling new approaches to design and program multispecies communities.  ...  This endeavor draws upon knowledge from synthetic biology, systems biology, microbial ecology and evolution.  ...  Furthermore, drawing realistic inferences from these models requires constraints for maximizing community-wide objective functions (e.g. graph-based tool that can identify thermodynamically-feasible biochemical  ... 
doi:10.1016/j.mib.2016.03.010 pmid:27084981 pmcid:PMC4899134 fatcat:7lgpy7kskvhpbhx5cb2gpxgl5m

Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

Bor-Sen Chen, Chia-Chou Wu
2013 Cells  
This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers.  ...  at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in  ...  F of the biochemical control circuit to be specified in Equation (4.15 ).  ... 
doi:10.3390/cells2040635 pmid:24709875 pmcid:PMC3972654 fatcat:iaby3nhu4zefdmeabagakufkmm

Design Automation for Synthetic Biological Systems

Douglas Densmore, Soha Hassoun
2012 IEEE Design & Test of Computers  
Editors' notes: Through principled engineering methods, synthetic biology aims to build specialized biological components that can be modularly composed to create complex systems.  ...  In addition, this work reflects numerous discussions with Ron Weiss, Jonathan Babb, Jacob Beal, Aaron Adler, Fusun Yaman, Swapnil Bhatia, and Traci Haddock, and with Kyongbum Lee, Gautham Sridharan, Ehsan  ...  An interesting feature of biochemical networks is that they exhibit a large number of possible functional states, resulting in a great variety of phenotypes.  ... 
doi:10.1109/mdt.2012.2193370 fatcat:zxaiso254bf63cxkskgdbatuti

Dynamic metabolic control: towards precision engineering of metabolism

Di Liu, Ahmad A. Mannan, Yichao Han, Diego A. Oyarzún, Fuzhong Zhang
2018 Journal of Industrial Microbiology & Biotechnology  
To overcome these problems, the last decade has 21 witnessed the emergence of a new technology that uses synthetic regulation to control 22 heterologous pathways dynamically, in ways akin to regulatory  ...  with the tools of synthetic 27 biology, can work to enhance microbial production. 28 29  ...  Taking the 59 concept of dynamic regulation, synthetic biologists have designed genetic circuits to dynamically 60 regulate engineered pathways for optimal biochemical production [73, 24, 18, 76, 37,  ... 
doi:10.1007/s10295-018-2013-9 pmid:29380150 fatcat:nc7sx54q6jdexemvx33cucgodq

In vitro regulatory models for systems biology

Anthony J. Genot, Teruo Fujii, Yannick Rondelez
2013 Biotechnology Advances  
We also recapitulate the lessons learned about in vivo biochemical circuits such as the importance of delays and competition, the links between topology and kinetics, as well as the intriguing resemblance  ...  We highlight how those efforts have culminated in the rational construction of biochemical oscillators and bistable memories in test tubes.  ...  YR also acknowledges support from the Grantin-Aid for Scientific Research on Priority Areas "Microfluidic platform for synthetic genetic circuits".  ... 
doi:10.1016/j.biotechadv.2013.04.008 pmid:23648627 fatcat:gr4mkdymmfgehhorqopcpp5sum

The context matrix: Navigating biological complexity for advanced biodesign

Camillo Moschner, Charlie Wedd, Somenath Bakshi
2022 Frontiers in Bioengineering and Biotechnology  
Synthetic biology offers many solutions in healthcare, production, sensing and agriculture.  ...  In this perspective article, we present the context matrix, a conceptual framework to categorise and explore these contexts and their net effect on the designed synthetic biosystem.  ...  Resource competition (top, middle panel), is the phenomenon of a synthetic circuit competing with the host genome for shared resources.  ... 
doi:10.3389/fbioe.2022.954707 pmid:36082163 pmcid:PMC9445834 fatcat:rwr6hz5tlfaytpabjnlqw67iqm

Contextualizing context for synthetic biology - identifying causes of failure of synthetic biological systems

Stefano Cardinale, Adam Paul Arkin
2012 Biotechnology Journal  
In this review, we set out to identify and classify the sources of the unexpected divergences between design and actual function of synthetic systems and analyze possible methodologies aimed at controlling  ...  in vivo.  ...  His current research focuses on the effect of each gene of the E. coli genome on cellular physiology and the activity of synthetic genetic circuits to identify key sources of failure of synthetic devices  ... 
doi:10.1002/biot.201200085 pmid:22649052 pmcid:PMC3440575 fatcat:4qnfzfrzu5hwdn3wyopvlbkzi4

Toward design-based engineering of industrial microbes

Keith EJ Tyo, Kanokarn Kocharin, Jens Nielsen
2010 Current Opinion in Microbiology  
As well, synthetic biology tools are melding modeling and molecular implementation.  ...  Recent advances in systems biology technologies have drastically improved the amount of information that can be collected in each iteration.  ...  Likewise, advances in Synthetic biology are allowing implementation of novel gene circuits that are guided by predictive models of each molecular 'part.'  ... 
doi:10.1016/j.mib.2010.02.001 pmid:20226723 pmcid:PMC2885540 fatcat:h527tb74breg7fkz2id2mwk47u

Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution

Yolanda Schaerli, Alba Jiménez, José M Duarte, Ljiljana Mihajlovic, Julien Renggli, Mark Isalan, James Sharpe, Andreas Wagner
2018 Molecular Systems Biology  
Here, we study evolutionary biases in two synthetic gene regulatory circuits expressed in Escherichia coli that produce a gene expression stripe -a pivotal pattern in embryonic development.  ...  The two parental circuits produce the same phenotype, but create it through different regulatory mechanisms.  ...  Here, we extended this approach to nonlinear GRNs by studying synthetic circuits in E. coli (Fig 1) .  ... 
doi:10.15252/msb.20178102 pmid:30201776 pmcid:PMC6129954 fatcat:sf63jhhvpzcgjipvtl3xqb7iy4

Use of Genome-Scale Metabolic Models in Evolutionary Systems Biology [chapter]

Balázs Papp, Balázs Szappanos, Richard A. Notebaart
2011 Msphere  
gene contents and phenotypes of yeast and other microbial species.  ...  While these studies have demonstrated that even simplified models of biochemical reaction networks can be highly informative for evolutionary analyses, they have also revealed the weakness of this modeling  ...  based on certain calculated phenotypes (e.g., identifying gene sets with correlated activities).  ... 
doi:10.1007/978-1-61779-173-4_27 pmid:21863504 fatcat:kxc2pko5xrhaplejlqhelrxd4q

Rewiring Cells: Synthetic Biology as a Tool to Interrogate the Organizational Principles of Living Systems

Caleb J. Bashor, Andrew A. Horwitz, Sergio G. Peisajovich, Wendell A. Lim
2010 Annual Review of Biophysics  
Here, we outline recent work that uses synthetic biology approaches to investigate the organization and function of cellular networks, and describe a vision for a synthetic biology toolkit that could be  ...  In addition, by building minimal toy networks, one can systematically explore the relationship between network structure and function.  ...  The search identified ∼400 robustly adapting circuits.  ... 
doi:10.1146/annurev.biophys.050708.133652 pmid:20192780 pmcid:PMC2965450 fatcat:je4bki77pfbtvadcq73lhxh3li

Modular cell design for rapid, efficient strain engineering toward industrialization of biology

Cong T Trinh, Brian Mendoza
2016 Current Opinion in Chemical Engineering  
The challenge is to develop microbial platforms to produce targeted chemicals with high efficiency in a rapid, predictable, and reproducible fashion.  ...  This paper highlights recent progress in rational design of heterologous pathways for combinatorial biosynthesis of a large space of chemicals and modular cell design for rapid strain engineering.  ...  The next critical step in heterologous pathway design is to identify parts that can be assembled to achieve optimal phenotypes.  ... 
doi:10.1016/j.coche.2016.07.005 fatcat:ieypyyetvbfolh2ard6yz4nvgu

Mapping the Environmental Fitness Landscape of a Synthetic Gene Circuit

Dmitry Nevozhay, Rhys M. Adams, Elizabeth Van Itallie, Matthew R. Bennett, Gábor Balázsi, Mario Andrea Marchisio
2012 PLoS Computational Biology  
To address this question we developed and quantitatively characterized an inducible, bistable synthetic gene circuit controlling the expression of a bifunctional antibiotic resistance gene in Saccharomyces  ...  Gene expression actualizes the organismal phenotypes encoded within the genome in an environment-dependent manner.  ...  Agarwal, and the participants of the ''Computation and Collective Behavior in Biological Systems'' workshop at the Aspen Center for Physics (June 2011) for valuable discussions.  ... 
doi:10.1371/journal.pcbi.1002480 pmid:22511863 pmcid:PMC3325171 fatcat:xzmm44paebbdrdrz4sskdqhrrm

Synthetic Mechanotransduction Using Engineered SynNotch Receptors [article]

D. Christopher Sloas, John T. Ngo
2022 bioRxiv   pre-print
This work provides insight regarding how mechanically-induced structural alterations in proteins can be used to transduce physical forces into biochemical signals, and the system should facilitate further  ...  The utility of these tools was demonstrated by the design of a decision-making circuit, through which fibroblasts could be made to differentiate into myoblasts in response to mechanostimulation with tensile  ...  Synthetic mechanogenetic circuits specify how cells interpret mechanical forces Using our collection of mechanosensitive receptors, we demonstrated further versatility in cellular outputs by designing  ... 
doi:10.1101/2022.05.01.490205 fatcat:cwnoo2eecvganmkmcusizvb6pa
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