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Computation gene circuits

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https://www.readbyqxmd.com/read/28801912/computational-sequence-design-with-r2odna-designer
#1
James T MacDonald, Velia Siciliano
Recently developed DNA assembly methods have enabled the rapid and simultaneous assembly of multiple parts to create complex synthetic gene circuits. A number of groups have proposed the use of computationally designed orthogonal spacer sequences to guide the ordered assembly of parts using overlap-directed or homologous recombination-based methods. This approach is particularly useful for assembling multiple parts with repetitive elements. Orthogonal spacer sequences (sometimes called UNSs-unique nucleotide sequences) also have a number of other potential uses including in the design of synthetic promoters regulated by novel regulatory elements...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28754589/mir-203a-controls-keratinocyte-proliferation-and-differentiation-via-targeting-the-stemness-associated-factor-%C3%AE-np63-and-establishing-a-regulatory-circuit-with-snai2
#2
Xu Ma, Ling Li, Tao Jia, Mingwei Chen, Guofeng Liu, Chunyang Li, Ning Li, Daping Yang
Keratinocyte differentiation plays a pivotal role in the function of epidermal barrier and can be triggered by extracellular calcium in vitro and in vivo, but the precise mechanism still need to be further investigated. On the other hand, it is known that microRNAs control multiple biological events including cellular proliferation and differentiation. The present study demonstrated that miR-203a expression was upregulated in calcium-induced HaCaT Cells in a dose-dependent manner, whereas the stemness-associated factors SNAI2 and ΔNp63 were downregulated...
July 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28750201/advancing-therapeutic-applications-of-synthetic-gene-circuits
#3
REVIEW
Yasutomi Higashikuni, William Cw Chen, Timothy K Lu
Synthetic biology aims to introduce new sense-and-respond capabilities into living cells, which would enable novel therapeutic strategies. The development of regulatory elements, molecular computing devices, and effector screening technologies has enabled researchers to design synthetic gene circuits in many organisms, including mammalian cells. Engineered gene networks, such as closed-loop circuits or Boolean logic gate circuits, can be used to program cells to perform specific functions with spatiotemporal control and restoration of homeostasis in response to the extracellular environment and intracellular signaling...
July 24, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28747874/the-functioning-of-a-cortex-without-layers
#4
REVIEW
Julien Guy, Jochen F Staiger
A major hallmark of cortical organization is the existence of a variable number of layers, i.e., sheets of neurons stacked on top of each other, in which neurons have certain commonalities. However, even for the neocortex, variable numbers of layers have been described and it is just a convention to distinguish six layers from each other. Whether cortical layers are a structural epiphenomenon caused by developmental dynamics or represent a functionally important modularization of cortical computation is still unknown...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28746304/complex-cellular-logic-computation-using-ribocomputing-devices
#5
Alexander A Green, Jongmin Kim, Duo Ma, Pamela A Silver, James J Collins, Peng Yin
Synthetic biology aims to develop engineering-driven approaches to the programming of cellular functions that could yield transformative technologies. Synthetic gene circuits that combine DNA, protein, and RNA components have demonstrated a range of functions such as bistability, oscillation, feedback, and logic capabilities. However, it remains challenging to scale up these circuits owing to the limited number of designable, orthogonal, high-performance parts, the empirical and often tedious composition rules, and the requirements for substantial resources for encoding and operation...
August 3, 2017: Nature
https://www.readbyqxmd.com/read/28742153/reconstructing-the-regulatory-circuit-of-cell-fate-determination-in-yeast-mating-response
#6
Bin Shao, Haiyu Yuan, Rongfei Zhang, Xuan Wang, Shuwen Zhang, Qi Ouyang, Nan Hao, Chunxiong Luo
Massive technological advances enabled high-throughput measurements of proteomic changes in biological processes. However, retrieving biological insights from large-scale protein dynamics data remains a challenging task. Here we used the mating differentiation in yeast Saccharomyces cerevisiae as a model and developed integrated experimental and computational approaches to analyze the proteomic dynamics during the process of cell fate determination. When exposed to a high dose of mating pheromone, the yeast cell undergoes growth arrest and forms a shmoo-like morphology; however, at intermediate doses, chemotropic elongated growth is initialized...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28709113/reprogramming-cellular-functions-with-engineered-membrane-proteins
#7
REVIEW
Caroline Arber, Melvin Young, Patrick Barth
Taking inspiration from Nature, synthetic biology utilizes and modifies biological components to expand the range of biological functions for engineering new practical devices and therapeutics. While early breakthroughs mainly concerned the design of gene circuits, recent efforts have focused on engineering signaling pathways to reprogram cellular functions. Since signal transduction across cell membranes initiates and controls intracellular signaling, membrane receptors have been targeted by diverse protein engineering approaches despite limited mechanistic understanding of their function...
July 11, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28680655/a-deterministic-method-for-estimating-free-energy-genetic-network-landscapes-with-applications-to-cell-commitment-and-reprogramming-paths
#8
Victor Olariu, Erica Manesso, Carsten Peterson
Depicting developmental processes as movements in free energy genetic landscapes is an illustrative tool. However, exploring such landscapes to obtain quantitative or even qualitative predictions is hampered by the lack of free energy functions corresponding to the biochemical Michaelis-Menten or Hill rate equations for the dynamics. Being armed with energy landscapes defined by a network and its interactions would open up the possibility of swiftly identifying cell states and computing optimal paths, including those of cell reprogramming, thereby avoiding exhaustive trial-and-error simulations with rate equations for different parameter sets...
June 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28586314/microrna-mediated-regulatory-circuits-outlook-and-perspectives
#9
REVIEW
Davide Cora', Angela Re, Michele Caselle, Federico Bussolino
MicroRNAs have been found to be necessary for regulating genes implicated in almost all signaling pathways, and consequently their dysfunction influences many diseases, including cancer. Understanding of the complexity of the microRNA-mediated regulatory network has grown in terms of size, connectivity and dynamics with the development of computational and, more recently, experimental high-throughput approaches for microRNA target identification. Newly developed studies on recurrent microRNA-mediated circuits in regulatory networks, also known as network motifs, have substantially contributed to addressing this complexity, and therefore to helping understand the ways by which microRNAs achieve their regulatory role...
June 6, 2017: Physical Biology
https://www.readbyqxmd.com/read/28540681/exploring-microrna-target-regulatory-interactions-by-computing-technologies
#10
Yue Hu, Wenjun Lan, Daniel Miller
MiRNA genes (miRNA precursor genes) share some common structural elements with protein genes. As with protein genes, the promoters of miRNA genes are necessary to regulate the expression of miRNA. The computation methods used to find the promoter regions of the protein genes have been applied to miRNA genes and some methods have been designed specifically to find the promoter regions of miRNA genes. The transcription factors (TFs), miRNA, and the targeted genes can form complex regulatory networks in the cells that can be divided into circuits...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28525642/dynamics-of-sequestration-based-gene-regulatory-cascades
#11
Tatenda Shopera, William R Henson, Tae Seok Moon
Gene regulatory cascades are ubiquitous in biology. Because regulatory cascades are integrated within complex networks, their quantitative analysis is challenging in native systems. Synthetic biologists have gained quantitative insights into the properties of regulatory cascades by building simple circuits, but sequestration-based regulatory cascades remain relatively unexplored. Particularly, it remains unclear how the cascade components collectively control the output dynamics. Here, we report the construction and quantitative analysis of the longest sequestration-based cascade in Escherichia coli...
May 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28494968/bistability-and-nonmonotonic-induction-of-the-lac-operon-in-the-natural-lactose-uptake-system
#12
Dominique Zander, Daniel Samaga, Ronny Straube, Katja Bettenbrock
The Escherichia coli lac operon is regulated by a positive feedback loop whose potential to generate an all-or-none response in single cells has been a paradigm for bistable gene expression. However, so far bistable lac induction has only been observed using gratuitous inducers, raising the question about the biological relevance of bistable lac induction in the natural setting with lactose as the inducer. In fact, the existing experimental evidence points to a graded rather than an all-or-none response in the natural lactose uptake system...
May 9, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28461722/systems-biology-study-of-transcriptional-and-post-transcriptional-co-regulatory-network-sheds-light-on-key-regulators-involved-in-important-biological-processes-in-citrus-sinensis
#13
Ehsan Khodadadi, Ali Ashraf Mehrabi, Ali Najafi, Saber Rastad, Ali Masoudi-Nejad
Transcriptional and post-transcriptional regulators including transcription regulator, transcription factor and miRNA are the main endogenous molecular elements which control complex cellular mechanisms such as development, growth and response to biotic and abiotic stresses in a coordinated manner in plants. Utilizing the most recent information on such relationships in a plant species, obtained from high-throughput experimental technologies and advanced computational tools, we can reconstruct its co-regulatory network which consequently sheds light on key regulators involved in its important biological processes...
April 2017: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
https://www.readbyqxmd.com/read/28459541/decoupling-resource-coupled-gene-expression-in-living-cells
#14
Tatenda Shopera, Lian He, Tolutola Oyetunde, Yinjie J Tang, Tae Seok Moon
Synthetic biology aspires to develop frameworks that enable the construction of complex and reliable gene networks with predictable functionalities. A key limitation is that increasing network complexity increases the demand for cellular resources, potentially causing resource-associated interference among noninteracting circuits. Although recent studies have shown the effects of resource competition on circuit behaviors, mechanisms that decouple such interference remain unclear. Here, we constructed three systems in Escherichia coli, each consisting of two independent circuit modules where the complexity of one module (Circuit 2) was systematically increased while the other (Circuit 1) remained identical...
May 4, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28455348/a-spectrum-of-modularity-in-multi-functional-gene-circuits
#15
Alba Jiménez, James Cotterell, Andreea Munteanu, James Sharpe
A major challenge in systems biology is to understand the relationship between a circuit's structure and its function, but how is this relationship affected if the circuit must perform multiple distinct functions within the same organism? In particular, to what extent do multi-functional circuits contain modules which reflect the different functions? Here, we computationally survey a range of bi-functional circuits which show no simple structural modularity: They can switch between two qualitatively distinct functions, while both functions depend on all genes of the circuit...
April 27, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28443619/programming-mrna-decay-to-modulate-synthetic-circuit-resource-allocation
#16
Ophelia S Venturelli, Mika Tei, Stefan Bauer, Leanne Jade G Chan, Christopher J Petzold, Adam P Arkin
Synthetic circuits embedded in host cells compete with cellular processes for limited intracellular resources. Here we show how funnelling of cellular resources, after global transcriptome degradation by the sequence-dependent endoribonuclease MazF, to a synthetic circuit can increase production. Target genes are protected from MazF activity by recoding the gene sequence to eliminate recognition sites, while preserving the amino acid sequence. The expression of a protected fluorescent reporter and flux of a high-value metabolite are significantly enhanced using this genome-scale control strategy...
April 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28437108/design-of-a-toolbox-of-rna-thermometers
#17
Shaunak Sen, Divyansh Apurva, Rohit Satija, Dan Siegal, Richard M Murray
Biomolecular temperature sensors can be used for efficient control of large-volume bioreactors, for spatiotemporal imaging and control of gene expression, and to engineer robustness to temperature in biomolecular circuit design. Although RNA-based sensors, called "thermometers", have been investigated in both natural and synthetic contexts, an important challenge is to design diverse responses to temperature differing in sensitivity and threshold. We address this issue by constructing a library of RNA thermometers based on thermodynamic computations and experimentally measuring their activities in cell-free biomolecular "breadboards"...
May 18, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28362798/interrogating-the-topological-robustness-of-gene-regulatory-circuits-by-randomization
#18
Bin Huang, Mingyang Lu, Dongya Jia, Eshel Ben-Jacob, Herbert Levine, Jose N Onuchic
One of the most important roles of cells is performing their cellular tasks properly for survival. Cells usually achieve robust functionality, for example, cell-fate decision-making and signal transduction, through multiple layers of regulation involving many genes. Despite the combinatorial complexity of gene regulation, its quantitative behavior has been typically studied on the basis of experimentally verified core gene regulatory circuitry, composed of a small set of important elements. It is still unclear how such a core circuit operates in the presence of many other regulatory molecules and in a crowded and noisy cellular environment...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28361666/towards-targeted-combinatorial-therapy-design-for-the-treatment-of-castration-resistant-prostate-cancer
#19
Osama Ali Arshad, Aniruddha Datta
BACKGROUND: Prostate cancer is one of the most prevalent cancers in males in the United States and amongst the leading causes of cancer related deaths. A particularly virulent form of this disease is castration-resistant prostate cancer (CRPC), where patients no longer respond to medical or surgical castration. CRPC is a complex, multifaceted and heterogeneous malady with limited standard treatment options. RESULTS: The growth and progression of prostate cancer is a complicated process that involves multiple pathways...
March 22, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28355056/deconvolution-of-gene-expression-noise-into-spatial-dynamics-of-transcription-factor-promoter-interplay
#20
Ángel Goñi-Moreno, Ilaria Benedetti, Juhyun Kim, Víctor de Lorenzo
Gene expression noise is not only the mere consequence of stochasticity, but also a signal that reflects the upstream physical dynamics of the cognate molecular machinery. Soil bacteria facing recalcitrant pollutants exploit noise of catabolic promoters to deploy beneficial phenotypes such as metabolic bet-hedging and/or division of biochemical labor. Although the role of upstream promoter-regulator interplay in the origin of this noise is little understood, its specifications are probably ciphered in flow cytometry data patterns...
April 17, 2017: ACS Synthetic Biology
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