5,310 research outputs found
Implications of Rewiring Bacterial Quorum Sensing
Bacteria employ quorum sensing, a form of cell-cell communication, to sense changes in population density and regulate gene expression accordingly. This work investigated the rewiring of one quorum-sensing module, the lux circuit from the marine bacterium Vibrio fischeri. Steady-state experiments demonstrate that rewiring the network architecture of this module can yield graded, threshold, and bistable gene expression as predicted by a mathematical model. The experiments also show that the native lux operon is most consistent with a threshold, as opposed to a bistable, response. Each of the rewired networks yielded functional population sensors at biologically relevant conditions, suggesting that this operon is particularly robust. These findings (i) permit prediction of the behaviors of quorum-sensing operons in bacterial pathogens and (ii) facilitate forward engineering of synthetic gene circuits
A Hierarchical Approach to Protein Molecular Evolution
Biological diversity has evolved despite the essentially infinite complexity
of protein sequence space. We present a hierarchical approach to the efficient
searching of this space and quantify the evolutionary potential of our approach
with Monte Carlo simulations. These simulations demonstrate that non-homologous
juxtaposition of encoded structure is the rate-limiting step in the production
of new tertiary protein folds. Non-homologous ``swapping'' of low energy
secondary structures increased the binding constant of a simulated protein by
relative to base substitution alone. Applications of our approach
include the generation of new protein folds and modeling the molecular
evolution of disease.Comment: 15 pages. 2 figures. LaTeX styl
Analytical study of the effect of recombination on evolution via DNA shuffling
We investigate a multi-locus evolutionary model which is based on the DNA
shuffling protocol widely applied in \textit{in vitro} directed evolution. This
model incorporates selection, recombination and point mutations. The simplicity
of the model allows us to obtain a full analytical treatment of both its
dynamical and equilibrium properties, for the case of an infinite population.
We also briefly discuss finite population size corrections
A co-occurrence framework conceptualized for bridging the gap between basic science, clinical research and clinical practices
The intellectual impulsiveness of man to understand the unknown and the continual need of the society to improve healthcare have encouraged extensive investigation on numerous and diverse cause-and-effect relationships. The nature of this endeavor, however, renders the inability of investigator at all levels to escape beyond the narrow conceptual boundary described by an early French philosopher as the vicious cycle. To enjoy the theoretically plausible benefits of refined labor division, data-driven healthcare management, and real-time evidence-based practices, it must first be acknowledged that co-occurrence is better than cause-and-effect in explaining how an observation takes place at a particular time. This paper details a co-occurrence framework, and discusses its implications for the global healthcare system
Mechanism of robust circadian oscillation of KaiC phosphorylation in vitro
By incubating the mixture of three cyanobacterial proteins, KaiA, KaiB, and
KaiC, with ATP in vitro, Kondo and his colleagues reconstituted the robust
circadian rhythm of the phosphorylation level of KaiC (Science, 308; 414-415
(2005)). This finding indicates that protein-protein interactions and the
associated hydrolysis of ATP suffice to generate the circadian rhythm. Several
theoretical models have been proposed to explain the rhythm generated in this
"protein-only" system, but the clear criterion to discern different possible
mechanisms was not known. In this paper, we discuss a model based on the two
basic assumptions: The assumption of the allosteric transition of a KaiC
hexamer and the assumption of the monomer exchange between KaiC hexamers. The
model shows a stable rhythmic oscillation of the phosphorylation level of KaiC,
which is robust against changes in concentration of Kai proteins. We show that
this robustness gives a clue to distinguish different possible mechanisms. We
also discuss the robustness of oscillation against the change in the system
size. Behaviors of the system with the cellular or subcellular size should shed
light on the role of the protein-protein interactions in in vivo circadian
oscillation
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