Predictable trends in protein noise.
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Gene Expression↗
Biomedical subjects
Mads Kaern
Publications and source records attributed to Mads Kaern.
Estimations of intrinsic and extrinsic noise in models of nonlinear genetic networks.
We discuss two methods that can be used to estimate the impact of internal and external variability on nonlinear systems, and demonstrate their utility by comparing two experimentally implemented oscillatory genetic networks with different designs. The methods allow for rapid estimations of intrinsic and extrinsic noise and should prove useful in the analysis of natural genetic networks and when constructing synthetic gene regulatory systems.
Animals↗
Physics takes another stab at biological design principles.
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Epigenesis, Genetic↗
Stochasticity in gene expression: from theories to phenotypes.
Genetically identical cells exposed to the same environmental conditions can show significant variation in molecular content and marked differences in phenotypic characteristics. This variability is linked to stochasticity in gene expression, which is generally viewed as having detrimental effects on cellular function with potential implications for disease. However, stochasticity in gene expression can also be advantageous. It can provide the flexibility needed by cells to adapt to fluctuating environments or respond to sudden stresses, and a mechanism by which population heterogeneity can be established during cellular differentiation and development.
Animals↗
Control of chemical pattern formation by a clock-and-wavefront type mechanism.
The segmentation of many animals ranging from insects to mammals involves the sequential formation of stationary stripes of gene expression that are perpendicular to the growth axis of the developing embryo. This process has been accounted for by a variety of theoretical "clock-and-wavefront" type models that involve the arrest of an oscillation (the clock) at a moving boundary (the wavefront). Here, we demonstrate experimentally that progressive arrest of a homogeneous oscillation can control the symmetry as well as the wavelength of spatial structures in a chemical system. We show how a spontaneously formed, labyrinthine pattern can be converted into a pattern composed of ordered, parallel stripes and confirm a previously predicted proportionality between the wavelength and the period of the homogeneous oscillation. Our experiments provide the first experimental demonstration of a general mechanism for the control of pattern formation that has been hypothesized to operate in the context of biological morphogenesis.
Animals↗
Programmable cells: interfacing natural and engineered gene networks.
Novel cellular behaviors and characteristics can be obtained by coupling engineered gene networks to the cell's natural regulatory circuitry through appropriately designed input and output interfaces. Here, we demonstrate how an engineered genetic circuit can be used to construct cells that respond to biological signals in a predetermined and programmable fashion. We employ a modular design strategy to create Escherichia coli strains where a genetic toggle switch is interfaced with: (i) the SOS signaling pathway responding to DNA damage, and (ii) a transgenic quorum sensing signaling pathway from Vibrio fischeri. The genetic toggle switch endows these strains with binary response dynamics and an epigenetic inheritance that supports a persistent phenotypic alteration in response to transient signals. These features are exploited to engineer cells that form biofilms in response to DNA-damaging agents and cells that activate protein synthesis when the cell population reaches a critical density. Our work represents a step toward the development of "plug-and-play" genetic circuitry that can be used to create cells with programmable behaviors.
DNA Damage↗
The engineering of gene regulatory networks.
The rapid accumulation of genetic information and advancement of experimental techniques have opened a new frontier in biomedical engineering. With the availability of well-characterized components from natural gene networks, the stage has been set for the engineering of artificial gene regulatory networks with sophisticated computational and functional capabilities. In these efforts, the ability to construct, analyze, and interpret qualitative and quantitative models is becoming increasingly important. In this review, we consider the current state of gene network engineering from a combined experimental and modeling perspective. We discuss how networks with increased complexity are being constructed from simple modular components and how quantitative deterministic and stochastic modeling of these modules may provide the foundation for accurate in silico representations of gene regulatory network function in vivo.
Animals↗
Stabilization of stationary excitation pulses in an open flow without long-range inhibition.
We study numerically and experimentally the stabilization of stationary excitation pulses in an open flow system. Since all the species have equal flow and diffusion coefficients, stabilization of stationary pulses by long-range inhibition is excluded. Upstream propagating pulses slow down as they approach the inflow boundary, where a constant forcing establishes a downstream extending subexcitable boundary layer. When the flow velocity is low, successive pulses vanish as they reach the subexcitable region. When the flow velocity is increased, the incoming pulses pile up near the inflow one after the other to form a stationary and space-periodic structure. This occurs in such a manner that the system remembers and stores the number of incoming pulses. We show that flow-induced stabilization of stationary pulses involves a mechanism by which the upstream subexcitable region and the flow cause the arrest of the pulse front and the pulse back, respectively. We discuss how the flow-stabilized structures compare to, and are different from those stabilized by a long-ranged, diffusive inhibition and from those observed in boundary-forced open flows of media showing relaxation-type oscillations.
Journal Article↗