Developments in the tools and methodologies of synthetic biology.

Synthetic biology is principally concerned with the rational design and engineering of biologically based parts, devices, or systems. However, biological systems are generally complex and unpredictable, and are therefore, intrinsically difficult to engineer. In order to address these fundamental challenges, synthetic biology is aiming to unify a body of knowledge from several foundational scientific fields, within the context of a set of engineering principles. This shift in perspective is enabling synthetic biologists to address complexity, such that robust biological systems can be designed, assembled, and tested as part of a biological design cycle. The design cycle takes a forward-design approach in which a biological system is specified, modeled, analyzed, assembled, and its functionality tested. At each stage of the design cycle, an expanding repertoire of tools is being developed. In this review, we highlight several of these tools in terms of their applications and benefits to the synthetic biology community

Color image processing in a cellular neural-network environment

When low-level hardware simulations of cellular neural networks (CNNs) are very costly for exploring new applications, the use of a behavioral simulator becomes indispensable. This paper presents a software prototype capable of performing image processing applications using CNNs. The software is based on a CNN multilayer structure in which each primary color is assigned to a unique layer. This allows an added flexibility as different processing applications can be performed in parallel. To be able to handle a full range of color tones, two novel color mapping schemes were derived. In the proposed schemes the color information is obtained from the cell's state rather than from its output. This modification is necessary because for many templates CNN has only binary stable outputs from which only either a fully saturated or a black color can be obtained. Additionally, a postprocessor capable of performing pixelwise logical operations among color layers was developed to enhance the results obtained from CNN. Examples in the areas of medical image processing, image restoration, and weather forecasting are provided to demonstrate the robustness of the software and the vast potential of CN

Diagrams as Vehicles for Scientific Reasoning

We argue that diagrams are not just a communicative tool but play important roles in the reasoning of biologists: in characterizing the phenomenon to be explained, identifying explanatory relations, and developing an account of the responsible mechanism. In the first two tasks diagrams facilitate applying visual processing to the detection of patterns that constitute phenomena or explanatory relations. Diagrams of a mechanism serve to guide reasoning about what parts and operations are needed and how potential parts of the mechanism are related to each other. Further they guide the development of computational models used to determine how the mechanism will behave. We illustrate each of these uses of diagrams with examples from research on circadian rhythm

Inhibitor binding mode and allosteric regulation of Na+-glucose symporters.

Sodium-dependent glucose transporters (SGLTs) exploit sodium gradients to transport sugars across the plasma membrane. Due to their role in renal sugar reabsorption, SGLTs are targets for the treatment of type 2 diabetes. Current therapeutics are phlorizin derivatives that contain a sugar moiety bound to an aromatic aglycon tail. Here, we develop structural models of human SGLT1/2 in complex with inhibitors by combining computational and functional studies. Inhibitors bind with the sugar moiety in the sugar pocket and the aglycon tail in the extracellular vestibule. The binding poses corroborate mutagenesis studies and suggest a partial closure of the outer gate upon binding. The models also reveal a putative Na+ binding site in hSGLT1 whose disruption reduces the transport stoichiometry to the value observed in hSGLT2 and increases inhibition by aglycon tails. Our work demonstrates that subtype selectivity arises from Na+-regulated outer gate closure and a variable region in extracellular loop EL5

ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data

<p>Abstract</p> <p>Background</p> <p>Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) or ChIP followed by genome tiling array analysis (ChIP-chip) have become standard technologies for genome-wide identification of DNA-binding protein target sites. A number of algorithms have been developed in parallel that allow identification of binding sites from ChIP-seq or ChIP-chip datasets and subsequent visualization in the University of California Santa Cruz (UCSC) Genome Browser as custom annotation tracks. However, summarizing these tracks can be a daunting task, particularly if there are a large number of binding sites or the binding sites are distributed widely across the genome.</p> <p>Results</p> <p>We have developed <it>ChIPpeakAnno </it>as a Bioconductor package within the statistical programming environment R to facilitate batch annotation of enriched peaks identified from ChIP-seq, ChIP-chip, cap analysis of gene expression (CAGE) or any experiments resulting in a large number of enriched genomic regions. The binding sites annotated with <it>ChIPpeakAnno </it>can be viewed easily as a table, a pie chart or plotted in histogram form, i.e., the distribution of distances to the nearest genes for each set of peaks. In addition, we have implemented functionalities for determining the significance of overlap between replicates or binding sites among transcription factors within a complex, and for drawing Venn diagrams to visualize the extent of the overlap between replicates. Furthermore, the package includes functionalities to retrieve sequences flanking putative binding sites for PCR amplification, cloning, or motif discovery, and to identify Gene Ontology (GO) terms associated with adjacent genes.</p> <p>Conclusions</p> <p><it>ChIPpeakAnno </it>enables batch annotation of the binding sites identified from ChIP-seq, ChIP-chip, CAGE or any technology that results in a large number of enriched genomic regions within the statistical programming environment R. Allowing users to pass their own annotation data such as a different Chromatin immunoprecipitation (ChIP) preparation and a dataset from literature, or existing annotation packages, such as <it>GenomicFeatures </it>and <it>BSgenom</it>e, provides flexibility. Tight integration to the <it>biomaRt </it>package enables up-to-date annotation retrieval from the BioMart database.</p

What's new pussycat? A genealogy of animal celebrity

Animal celebrity is a human creation informing us about our socially constructed natural world. It is relational, expressive of cultural proclivities, political power plays and the quotidian everyday, as well as serious philosophical reflections on the meaning of being human. This article attempts to outline some key contours in the genealogy of animal celebrity, showing how popular culture, including fairground attractions, public relations, Hollywood movies, documentary films, zoo attractions, commercial sport and mediatised moral panics - particularly those accompanying scientific developments such as cloning - help to order, categorise and license aspects of human understanding and feelings. The nature of [animal] charisma and celebrity are explored with assistance from Jumbo the Elephant, Guy the Gorilla, Paul the clairvoyant octopus, Uggie the film star, Nénette the orang-utan and Dolly the sheep. It argues that the issue of what it is to be human lies beneath the celebritised surface or, as Donna Haraway noted, the issue 'of having to face oneself'

Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction.

The AAA protein Msp1 extracts mislocalized tail-anchored membrane proteins and targets them for degradation, thus maintaining proper cell organization. How Msp1 selects its substrates and firmly engages them during the energetically unfavorable extraction process remains a mystery. To address this question, we solved cryo-EM structures of Msp1-substrate complexes at near-atomic resolution. Akin to other AAA proteins, Msp1 forms hexameric spirals that translocate substrates through a central pore. A singular hydrophobic substrate recruitment site is exposed at the spiral's seam, which we propose positions the substrate for entry into the pore. There, a tight web of aromatic amino acids grips the substrate in a sequence-promiscuous, hydrophobic milieu. Elements at the intersubunit interfaces coordinate ATP hydrolysis with the subunits' positions in the spiral. We present a comprehensive model of Msp1's mechanism, which follows general architectural principles established for other AAA proteins yet specializes Msp1 for its unique role in membrane protein extraction