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Computation gene circuits

Miriam Leon, Mae L Woods, Alex J H Fedorec, Chris P Barnes
BACKGROUND: Genetic switches exhibit multistability, form the basis of epigenetic memory, and are found in natural decision making systems, such as cell fate determination in developmental pathways. Synthetic genetic switches can be used for recording the presence of different environmental signals, for changing phenotype using synthetic inputs and as building blocks for higher-level sequential logic circuits. Understanding how multistable switches can be constructed and how they function within larger biological systems is therefore key to synthetic biology...
December 7, 2016: BMC Systems Biology
Sufang Li, Yihong Yang, Ewa Hoffmann, Rachel F Tyndale, Elliot A Stein
BACKGROUND: Variation in the CYP2A6 gene alters the rate of nicotine metabolic inactivation and is associated with smoking behaviors and cessation success rates. The underlying neurobiological mechanisms of this genetic influence are unknown. METHODS: Intrinsic functional connectivity strength, a whole-brain, data-driven, graph theory-based method, was applied to resting-state functional magnetic resonance imaging data in 66 smokers and 92 nonsmokers. A subset of subjects (n = 23/20; smokers/nonsmokers) performed the monetary incentive delay task, probing reward anticipation, and a go/no-go task, probing response inhibition, on two occasions, in the presence and absence of a nicotine patch...
September 28, 2016: Biological Psychiatry
Stephanie Grehl, David Martina, Catherine Goyenvalle, Zhi-De Deng, Jennifer Rodger, Rachel M Sherrard
Non-invasive brain stimulation (NIBS) by electromagnetic fields appears to benefit human neurological and psychiatric conditions, although the optimal stimulation parameters and underlying mechanisms remain unclear. Although, in vitro studies have begun to elucidate cellular mechanisms, stimulation is delivered by a range of coils (from commercially available human stimulation coils to laboratory-built circuits) so that the electromagnetic fields induced within the tissue to produce the reported effects are ill-defined...
2016: Frontiers in Neural Circuits
Peter B Winter, Renee M Brielmann, Nicholas P Timkovich, Helio T Navarro, Andreia Teixeira-Castro, Richard I Morimoto, Luis A N Amaral
The study of C. elegans has led to ground-breaking discoveries in gene-function, neuronal circuits, and physiological responses. Subtle behavioral phenotypes, however, are often difficult to measure reproducibly. We have developed an experimental and computational infrastructure to simultaneously record and analyze the physical characteristics, movement, and social behaviors of dozens of interacting free-moving nematodes. Our algorithm implements a directed acyclic network that reconstructs the complex behavioral trajectories generated by individual C...
October 11, 2016: Scientific Reports
Namasivayam Ravi, Luis Sanchez-Guardado, Carlos Lois, Wolfgang Kelsch
The mammalian olfactory bulb is a forebrain structure just one synapse downstream from the olfactory sensory neurons and performs the complex computations of sensory inputs. The formation of this sensory circuit is shaped through activity-dependent and cell-intrinsic mechanisms. Recent studies have revealed that cell-type specific connectivity and the organization of synapses in dendritic compartments are determined through cell-intrinsic programs already preset in progenitor cells. These progenitor programs give rise to subpopulations within a neuron type that have distinct synaptic organizations...
September 30, 2016: Cellular and Molecular Life Sciences: CMLS
Romina D'Aurizio, Francesco Russo, Elena Chiavacci, Mario Baumgart, Marco Groth, Mara D'Onofrio, Ivan Arisi, Giuseppe Rainaldi, Letizia Pitto, Marco Pellegrini
MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in the post-transcriptional regulation of gene expression. miRNAs are involved in the regulation of many biological processes such as differentiation, apoptosis, and cell proliferation. miRNAs are expressed in embryonic, postnatal, and adult hearts, and they have a key role in the regulation of gene expression during cardiovascular development and disease. Aberrant expression of miRNAs is associated with abnormal cardiac cell differentiation and dysfunction...
2016: Frontiers in Bioengineering and Biotechnology
Robert W Bradley, Martin Buck, Baojun Wang
A central aim of synthetic biology is to build organisms that can perform useful activities in response to specified conditions. The digital computing paradigm which has proved so successful in electrical engineering is being mapped to synthetic biological systems to allow them to make such decisions. However, stochastic molecular processes have graded input-output functions, thus, bioengineers must select those with desirable characteristics and refine their transfer functions to build logic gates with digital-like switching behaviour...
October 2016: Current Opinion in Microbiology
Hojin Lee, Won Chan Oh, Jihye Seong, Jinhyun Kim
The complex information-processing capabilities of the central nervous system emerge from intricate patterns of synaptic input-output relationships among various neuronal circuit components. Understanding these capabilities thus requires a precise description of the individual synapses that comprise neural networks. Recent advances in fluorescent protein engineering, along with developments in light-favoring tissue clearing and optical imaging techniques, have rendered light microscopy (LM) a potent candidate for large-scale analyses of synapses, their properties, and their connectivity...
2016: Frontiers in Synaptic Neuroscience
A J Genot, A Baccouche, R Sieskind, N Aubert-Kato, N Bredeche, J F Bartolo, V Taly, T Fujii, Y Rondelez
Analog molecular circuits can exploit the nonlinear nature of biochemical reaction networks to compute low-precision outputs with fewer resources than digital circuits. This analog computation is similar to that employed by gene-regulation networks. Although digital systems have a tractable link between structure and function, the nonlinear and continuous nature of analog circuits yields an intricate functional landscape, which makes their design counter-intuitive, their characterization laborious and their analysis delicate...
August 2016: Nature Chemistry
Irene Otero-Muras, David Henriques, Julio R Banga
MOTIVATION: The design of de novo circuits with predefined performance specifications is a challenging problem in Synthetic Biology. Computational models and tools have proved to be crucial for a successful wet lab implementation. Natural gene circuits are complex, subject to evolutionary tradeoffs and playing multiple roles. However, most synthetic designs implemented to date are simple and perform a single task. As the field progresses, advanced computational tools are needed in order to handle greater levels of circuit complexity in a more flexible way and considering multiple design criteria...
July 8, 2016: Bioinformatics
Hui Liu, Gene E Robinson, Eric Jakobsson
The emerging field of sociogenomics explores the relations between social behavior and genome structure and function. An important question is the extent to which associations between social behavior and gene expression are conserved among the Metazoa. Prior experimental work in an invertebrate model of social behavior, the honey bee, revealed distinct brain gene expression patterns in African and European honey bees, and within European honey bees with different behavioral phenotypes. The present work is a computational study of these previous findings in which we analyze, by orthology determination, the extent to which genes that are socially regulated in honey bees are conserved across the Metazoa...
June 2016: PLoS Computational Biology
Nicolas Perry, Edward M Nelson, Gregory Timp
The promise of adapting biology to information processing will not be realized until engineered gene circuits, operating in different cell populations, can be wired together to express a predictable function. Here, elementary biological integrated circuits (BICs), consisting of two sets of transmitter and receiver gene circuit modules with embedded memory placed in separate cell populations, were meticulously assembled using live cell lithography and wired together by the mass transport of quorum-sensing (QS) signal molecules to form two isolated communication links (comlinks)...
December 16, 2016: ACS Synthetic Biology
Morgan Madec, Fran├žois Pecheux, Yves Gendrault, Elise Rosati, Christophe Lallement, Jacques Haiech
The topic of this article is the development of an open-source automated design framework for synthetic biology, specifically for the design of artificial gene regulatory networks based on a digital approach. In opposition to other tools, GeNeDA is an open-source online software based on existing tools used in microelectronics that have proven their efficiency over the last 30 years. The complete framework is composed of a computation core directly adapted from an Electronic Design Automation tool, input and output interfaces, a library of elementary parts that can be achieved with gene regulatory networks, and an interface with an electrical circuit simulator...
October 2016: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
June I Medford, Ashok Prasad
Synthetic biology enables the construction of genetic circuits with predictable gene functions in plants. Detailed quantitative descriptions of the transfer function or input-output function for genetic parts (promoters, 5' and 3' untranslated regions, etc.) are collected. These data are then used in computational simulations to determine their robustness and desired properties, thereby enabling the best components to be selected for experimental testing in plants. In addition, the process forms an iterative workflow which allows vast improvement to validated elements with sub-optimal function...
July 2016: Plant Journal: for Cell and Molecular Biology
Jacob R Rubens, Gianluca Selvaggio, Timothy K Lu
Living cells implement complex computations on the continuous environmental signals that they encounter. These computations involve both analogue- and digital-like processing of signals to give rise to complex developmental programs, context-dependent behaviours and homeostatic activities. In contrast to natural biological systems, synthetic biological systems have largely focused on either digital or analogue computation separately. Here we integrate analogue and digital computation to implement complex hybrid synthetic genetic programs in living cells...
2016: Nature Communications
Maya Botzman, Aharon Nachshon, Avital Brodt, Irit Gat-Viks
MOTIVATION: Expression Quantitative Trait Locus (eQTL) mapping tackles the problem of identifying variation in DNA sequence that have an effect on the transcriptional regulatory network. Major computational efforts are aimed at characterizing the joint effects of several eQTLs acting in concert to govern the expression of the same genes. Yet, progress toward a comprehensive prediction of such joint effects is limited. For example, existing eQTL methods commonly discover interacting loci affecting the expression levels of a module of co-regulated genes...
2016: Frontiers in Genetics
Evgeni V Nikolaev, Eduardo D Sontag
Synthetic constructs in biotechnology, biocomputing, and modern gene therapy interventions are often based on plasmids or transfected circuits which implement some form of "on-off" switch. For example, the expression of a protein used for therapeutic purposes might be triggered by the recognition of a specific combination of inducers (e.g., antigens), and memory of this event should be maintained across a cell population until a specific stimulus commands a coordinated shut-off. The robustness of such a design is hampered by molecular ("intrinsic") or environmental ("extrinsic") noise, which may lead to spontaneous changes of state in a subset of the population and is reflected in the bimodality of protein expression, as measured for example using flow cytometry...
April 2016: PLoS Computational Biology
Mark S Cembrowski, Lihua Wang, Ken Sugino, Brenda C Shields, Nelson Spruston
Clarifying gene expression in narrowly defined neuronal populations can provide insight into cellular identity, computation, and functionality. Here, we used next-generation RNA sequencing (RNA-seq) to produce a quantitative, whole genome characterization of gene expression for the major excitatory neuronal classes of the hippocampus; namely, granule cells and mossy cells of the dentate gyrus, and pyramidal cells of areas CA3, CA2, and CA1. Moreover, for the canonical cell classes of the trisynaptic loop, we profiled transcriptomes at both dorsal and ventral poles, producing a cell-class- and region-specific transcriptional description for these populations...
April 26, 2016: ELife
Gianfranco Politano, Francesca Orso, Monica Raimo, Alfredo Benso, Alessandro Savino, Daniela Taverna, Stefano Di Carlo
BACKGROUND: Biological research increasingly relies on network models to study complex phenomena. Signal Transduction Pathways are molecular circuits that model how cells receive, process, and respond to information from the environment providing snapshots of the overall cell dynamics. Most of the attempts to reconstruct signal transduction pathways are limited to single regulator networks including only genes/proteins. However, networks involving a single type of regulator and neglecting transcriptional and post-transcriptional regulations mediated by transcription factors and microRNAs, respectively, may not fully reveal the complex regulatory mechanisms of a cell...
April 8, 2016: BMC Bioinformatics
Ganhui Lan, Yuhai Tu
Living systems have to constantly sense their external environment and adjust their internal state in order to survive and reproduce. Biological systems, from as complex as the brain to a single E. coli cell, have to process these data in order to make appropriate decisions. How do biological systems sense external signals? How do they process the information? How do they respond to signals? Through years of intense study by biologists, many key molecular players and their interactions have been identified in different biological machineries that carry out these signaling functions...
May 2016: Reports on Progress in Physics
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