Synthetic biology: new engineering rules for an emerging discipline

Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development

An engineered mammalian band-pass network

Gene expression circuitries, which enable cells to detect precise levels within a morphogen concentration gradient, have a pivotal impact on biological processes such as embryonic pattern formation, paracrine and autocrine signalling, and cellular migration. We present the rational synthesis of a synthetic genetic circuit exhibiting band-pass detection characteristics. The components, involving multiply linked mammalian trans-activator and -repressor control systems, were selected and fine-tuned to enable the detection of ‘low-threshold’ morphogen (tetracycline) concentrations, in which target gene expression was triggered, and a ‘high-threshold’ concentration, in which expression was muted. In silico predictions and supporting experimental findings indicated that the key criterion for functional band-pass detection was the matching of componentry that enabled sufficient separation of the low and high threshold points. Using the circuitry together with a fluorescence-encoded target gene, mammalian cells were genetically engineered to be capable of forming a band-like pattern of differentiation in response to a tetracycline chemical gradient. Synthetic gene networks designed to emulate naturally occurring gene behaviours provide not only insight into biological processes, but may also foster progress in future tissue engineering, gene therapy and biosensing applications

Geological interpretation of volcanism and segmentation of the Mariana back-arc spreading center between 12.7°N and 18.3°N

The relationships between tectonic processes, magmatism, and hydrothermal venting along ∼600 km of the slow-spreading Mariana back-arc between 12.7°N and 18.3°N reveal a number of similarities and differences compared to slow-spreading mid-ocean ridges. Analysis of the volcanic geomorphology and structure highlights the complexity of the back-arc spreading center. Here, ridge segmentation is controlled by large-scale basement structures that appear to predate back-arc rifting. These structures also control the orientation of the chains of cross-arc volcanoes that characterize this region. Segment-scale faulting is oriented perpendicular to the spreading direction, allowing precise spreading directions to be determined. Four morphologically distinct segment types are identified: dominantly magmatic segments (Type I); magmatic segments currently undergoing tectonic extension (Type II); dominantly tectonic segments (Type III); and tectonic segments currently undergoing magmatic extension (Type IV). Variations in axial morphology (including eruption styles, neovolcanic eruption volumes, and faulting) reflect magma supply, which is locally enhanced by cross-arc volcanism associated with N-S compression along the 16.5°N and 17.0°N segments. In contrast, cross-arc seismicity is associated with N-S extension and increased faulting along the 14.5°N segment, with structures that are interpreted to be oceanic core complexes—the first with high-resolution bathymetry described in an active back-arc basin. Hydrothermal venting associated with recent magmatism has been discovered along all segment types

An Environment-Sensitive Synthetic Microbial Ecosystem

Microbial ecosystems have been widely used in industrial production, but the inter-relationships of organisms within them haven't been completely clarified due to complex composition and structure of natural microbial ecosystems. So it is challenging for ecologists to get deep insights on how ecosystems function and interplay with surrounding environments. But the recent progresses in synthetic biology show that construction of artificial ecosystems where relationships of species are comparatively clear could help us further uncover the meadow of those tiny societies. By using two quorum-sensing signal transduction circuits, this research designed, simulated and constructed a synthetic ecosystem where various population dynamics formed by changing environmental factors. Coherent experimental data and mathematical simulation in our study show that different antibiotics levels and initial cell densities can result in correlated population dynamics such as extinction, obligatory mutualism, facultative mutualism and commensalism. This synthetic ecosystem provides valuable information for addressing questions in ecology and may act as a chassis for construction of more complex microbial ecosystems

Timescales for the growth of sediment diapirs in subduction zones

Author Posting. © The Author(s), 2012. This article is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Geophysical Journal International 190 (2012): 1361–1377, doi:10.1111/j.1365-246X.2012.05565.x.In this study, we calculate timescales for the growth of gravitational instabilities forming in the sediment layer on the downgoing slab at subduction zones. Subducted metasediments are buoyant with respect to the overlying mantle and may form diapirs that detach from the slab and rise upwards into the mantle wedge. We use a particle-in-cell, finite-difference method to calculate growth rates for instabilities forming within a buoyant, wet-quartz metasediment layer underlying a dense mantle half-space composed of wet olivine. These growth rates are used to determine where sediment diapirs initiate and detach from the slab over a range of subduction zone thermal structures. We find that, given a sufficient layer thickness (200–800 m, depending on slab-surface and mantle-wedge temperatures), sediment diapirs begin to grow rapidly at depths of ∼80 km and detach from the slab within 1–3 Myr at temperatures ≤900 °C and at depths roughly corresponding to the location of the slab beneath the arc. Diapir growth is most sensitive to absolute slab temperature, however it is also affected by the viscosity ratio between the sediment layer and the mantle wedge and the length-scale over which viscosity decays above the slab. These secondary affects are most pronounced in colder subduction systems with old slabs and faster subduction rates. For a broad range of subduction zone thermal conditions, we find that diapirs can efficiently transport sediments into the mantle wedge, where they would melt and be incorporated into arc magmas. Thus, we conclude that sediment diapirism is a common feature of many subduction zones, providing a potential explanation for the ‘sediment signature’ in the chemistry of arc magmas.This work was supported by NSF Grant EAR-0652707 and a WHOI Deep Ocean Exploration Institute Fellowship to MB

Limits of the seismogenic zone in the epicentral region of the 26 December 2004 great Sumatra-Andaman earthquake: Results from seismic refraction and wide-angle reflection surveys and thermal modeling

The 26 December 2004 Sumatra earthquake (Mw = 9.1) initiated around 30 km depth and ruptured 1300 km of the Indo-Australian Sunda plate boundary. During the Sumatra OBS (ocean bottom seismometer) survey, a wide angle seismic profile was acquired across the epicentral region. A seismic velocity model was obtained from combined travel time tomography and forward modeling. Together with reflection seismic data from the SeaCause II cruise, the deep structure of the source region of the great earthquake is revealed. Four to five kilometers of sediments overlie the oceanic crust at the trench, and the subducting slab can be imaged down to a depth of 35 km. We find a crystalline backstop 120 km from the trench axis, below the fore arc basin. A high velocity zone at the lower landward limit of the raycovered domain, at 22 km depth, marks a shallow continental Moho, 170 km from the trench. The deep structure obtained from the seismic data was used to construct a thermal model of the fore arc in order to predict the limits of the seismogenic zone along the plate boundary fault. Assuming 100C-150C as its updip limit, the seismogenic zone is predicted to begin 530 km from the trench. The downdip limit of the 2004 rupture as inferred from aftershocks is within the 350C 450C temperature range, but this limit is 210-250 km from the trench axis and is much deeper than the fore arc Moho. The deeper part of the rupture occurred along the contact between the mantle wedge and the downgoing plate

Phylogeography of Supralittoral Rocky Intertidal Ligia Isopods in the Pacific Region from Central California to Central Mexico

Ligia isopods are widely distributed in the Pacific rocky intertidal shores from central California to central Mexico, including the Gulf of California. Yet, their biological characteristics restrict them to complete their life cycles in a very narrow range of the rocky intertidal supralittoral. Herein, we examine phylogeographic patterns of Ligia isopods from 122 localities between central California and central Mexico. We expect to find high levels of allopatric diversity. In addition, we expect the phylogeographic patterns to show signatures of past vicariant events that occurred in this geologically dynamic region.We sequenced two mitochondrial genes (Cytochrome Oxidase I and 16S ribosomal DNA). We conducted Maximum Likelihood and Bayesian phylogenetic analyses. We found many divergent clades that, in general, group according to geography. Some of the most striking features of the Ligia phylogeographic pattern include: (1) deep mid-peninsular phylogeographic breaks on the Pacific and Gulf sides of Baja peninsula; (2) within the Gulf lineages, the northern peninsula is most closely related to the northern mainland, while the southern peninsula is most closely related to the central-southern mainland; and, (3) the southernmost portion of the peninsula (Cape Region) is most closely related to the southernmost portion of mainland.Our results shed light on the phylogenetic relationships of Ligia populations in the study area. This study probably represents the finest-scale phylogeographic examination for any organism to date in this region. Presence of highly divergent lineages suggests multiple Ligia species exist in this region. The phylogeographic patterns of Ligia in the Gulf of California and Baja peninsula are incongruent with a widely accepted vicariant scenario among phylogeographers, but consistent with aspects of alternative geological hypotheses and phylo- and biogeographic patterns of several other taxa. Our findings contribute to the ongoing debate regarding the geological origin of this important biogeographic region