634 research outputs found
A Standard Parts List for Biological Circuitry
One of the hallmarks of biochemical circuits found in nature is analog, asymmetric, asynchronous design. That
is, there is little standardization of parts, e.g. all the promoters have different strengths and kinetics,
transcription factors are designed to have different effects at different loci, and each enzymatic reaction has its own
idiosyncratic mechanism and rates. In addition, all of the heterogeneous circuit elements are executing their
functions concurrently and asynchronously. Biological circuits are seemingly designed to deal with the
fluctuating delays, different time-scales and energy requirements associated with each component process of the
overall network. These factors also make design of novel biochemical circuitry from existent parts difficult to
achieve. Without standardization, the qualitative design methods used in other engineering fields are simply
inapplicable. The de facto design methodology for biological circuitry is natural selection. Rational design of
biological systems by humans has remained restricted to rather small or hit-or-miss efforts and has often relied
on the ability to "select" for biochemical parts that fulfill some criteria. In practice however biological-designers
are rare, and solutions are usually realized through an expensive stepwise trial and error approach or through
mutation and selection. Furthermore, these otherwise practical approaches are limited in terms of the problems
they can solve. We believe that implementation of designed biological circuitry is limited by issues of practice
Fundamental Limits to Position Determination by Concentration Gradients
Position determination in biological systems is often achieved through
protein concentration gradients. Measuring the local concentration of such a
protein with a spatially-varying distribution allows the measurement of
position within the system. In order for these systems to work effectively,
position determination must be robust to noise. Here, we calculate fundamental
limits to the precision of position determination by concentration gradients
due to unavoidable biochemical noise perturbing the gradients. We focus on
gradient proteins with first order reaction kinetics. Systems of this type have
been experimentally characterised in both developmental and cell biology
settings. For a single gradient we show that, through time-averaging, great
precision can potentially be achieved even with very low protein copy numbers.
As a second example, we investigate the ability of a system with oppositely
directed gradients to find its centre. With this mechanism, positional
precision close to the centre improves more slowly with increasing averaging
time, and so longer averaging times or higher copy numbers are required for
high precision. For both single and double gradients, we demonstrate the
existence of optimal length scales for the gradients, where precision is
maximized, as well as analyzing how precision depends on the size of the
concentration measuring apparatus. Our results provide fundamental constraints
on the positional precision supplied by concentration gradients in various
contexts, including both in developmental biology and also within a single
cell.Comment: 24 pages, 2 figure
Towards synthetic biological approaches to resource utilization on space missions.
This paper demonstrates the significant utility of deploying non-traditional biological techniques to harness available volatiles and waste resources on manned missions to explore the Moon and Mars. Compared with anticipated non-biological approaches, it is determined that for 916 day Martian missions: 205 days of high-quality methane and oxygen Mars bioproduction with Methanobacterium thermoautotrophicum can reduce the mass of a Martian fuel-manufacture plant by 56%; 496 days of biomass generation with Arthrospira platensis and Arthrospira maxima on Mars can decrease the shipped wet-food mixed-menu mass for a Mars stay and a one-way voyage by 38%; 202 days of Mars polyhydroxybutyrate synthesis with Cupriavidus necator can lower the shipped mass to three-dimensional print a 120 m(3) six-person habitat by 85% and a few days of acetaminophen production with engineered Synechocystis sp. PCC 6803 can completely replenish expired or irradiated stocks of the pharmaceutical, thereby providing independence from unmanned resupply spacecraft that take up to 210 days to arrive. Analogous outcomes are included for lunar missions. Because of the benign assumptions involved, the results provide a glimpse of the intriguing potential of 'space synthetic biology', and help focus related efforts for immediate, near-term impact
Fast, cheap and somewhat in control
Efforts to manipulate living organisms have raised the question of whether engineering principles of hierarchy, abstraction and design can be applied to biological systems. Here, we consider the practical challenges to controlling living organisms that must be surmounted, or at least managed, if synthetic biology and cellular bioengineering are to be productive
The genetic basis of energy conservation in the sulfate-reducing bacterium Desulfovibrio alaskensis G20.
Sulfate-reducing bacteria play major roles in the global carbon and sulfur cycles, but it remains unclear how reducing sulfate yields energy. To determine the genetic basis of energy conservation, we measured the fitness of thousands of pooled mutants of Desulfovibrio alaskensis G20 during growth in 12 different combinations of electron donors and acceptors. We show that ion pumping by the ferredoxin:NADH oxidoreductase Rnf is required whenever substrate-level phosphorylation is not possible. The uncharacterized complex Hdr/flox-1 (Dde_1207:13) is sometimes important alongside Rnf and may perform an electron bifurcation to generate more reduced ferredoxin from NADH to allow further ion pumping. Similarly, during the oxidation of malate or fumarate, the electron-bifurcating transhydrogenase NfnAB-2 (Dde_1250:1) is important and may generate reduced ferredoxin to allow additional ion pumping by Rnf. During formate oxidation, the periplasmic [NiFeSe] hydrogenase HysAB is required, which suggests that hydrogen forms in the periplasm, diffuses to the cytoplasm, and is used to reduce ferredoxin, thus providing a substrate for Rnf. During hydrogen utilization, the transmembrane electron transport complex Tmc is important and may move electrons from the periplasm into the cytoplasmic sulfite reduction pathway. Finally, mutants of many other putative electron carriers have no clear phenotype, which suggests that they are not important under our growth conditions, although we cannot rule out genetic redundancy
A mass conserved reaction-diffusion system captures properties of cell polarity
Various molecules exclusively accumulate at the front or back of migrating
eukaryotic cells in response to a shallow gradient of extracellular signals.
Directional sensing and signal amplification highlight the essential properties
in the migrating cells, known as cell polarity. In addition to these, such
properties of cell polarity involve unique determination of migrating direction
(uniqueness of axis) and localized gradient sensing at the front edge
(localization of sensitivity), both of which may be required for smooth
migration. Here we provide the mass conservation system based on the
reaction-diffusion system with two components, where the mass of the two
components is always conserved. Using two models belonging to this mass
conservation system, we demonstrate through both numerical simulation and
analytical approximations that the spatial pattern with a single peak
(uniqueness of axis) can be generally observed and that the existent peak
senses a gradient of parameters at the peak position, which guides the movement
of the peak. We extended this system with multiple components, and we developed
a multiple-component model in which cross-talk between members of the Rho
family of small GTPases is involved. This model also exhibits the essential
properties of the two models with two components. Thus, the mass conservation
system shows properties similar to those of cell polarity, such as uniqueness
of axis and localization of sensitivity, in addition to directional sensing and
signal amplification.Comment: PDF onl
Stochastic Gene Expression in a Lentiviral Positive Feedback Loop: HIV-1 Tat Fluctuations Drive Phenotypic Diversity
Stochastic gene expression has been implicated in a variety of cellular
processes, including cell differentiation and disease. In this issue of Cell,
Weinberger et al. (2005) take an integrated computational-experimental approach
to study the Tat transactivation feedback loop in HIV-1 and show that
fluctuations in a key regulator, Tat, can result in a phenotypic bifurcation.
This phenomenon is observed in an isogenic population where individual cells
display two distinct expression states corresponding to latent and productive
infection by HIV-1. These findings demonstrate the importance of stochastic
gene expression in molecular "decision-making."Comment: Supplemental data available as q-bio.MN/060800
Draft Genome Sequence for Desulfovibrio africanus Strain PCS.
Desulfovibrio africanus strain PCS is an anaerobic sulfate-reducing bacterium (SRB) isolated from sediment from Paleta Creek, San Diego, CA. Strain PCS is capable of reducing metals such as Fe(III) and Cr(VI), has a cell cycle, and is predicted to produce methylmercury. We present the D. africanus PCS genome sequence
Evolution, ecology and the engineered organism: lessons for synthetic biology
An understanding of evolution and ecology will be critical to the success of synthetic biology
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