Transition from amplitude to oscillation death via Turing bifurcation.

Coupled oscillators are shown to experience two structurally different oscillation quenching types: amplitude death (AD) and oscillation death (OD). We demonstrate that both AD and OD can occur in one system and find that the transition between them underlies a classical, Turing-type bifurcation, providing a clear classification of these significantly different dynamical regimes. The implications of obtaining a homogeneous (AD) or inhomogeneous (OD) steady state, as well as their significance for physical and biological applications and control studies, are also pointed out.

An electronic analog of synthetic genetic networks.

An electronic analog of a synthetic genetic network known as the repressilator is proposed. The repressilator is a synthetic biological clock consisting of a cyclic inhibitory network of three negative regulatory genes which produces oscillations in the expressed protein concentrations. Compared to previous circuit analogs of the repressilator, the circuit here takes into account more accurately the kinetics of gene expression, inhibition, and protein degradation. A good agreement between circuit measurements and numerical prediction is observed. The circuit allows for easy control of the kinetic parameters thereby aiding investigations of large varieties of potential dynamics.

Multistability of synthetic genetic networks with repressive cell-to-cell communication.

We investigate an experimentally feasible synthetic genetic network consisting of two phase repulsively coupled repressilators, which evokes multiple coexisting stable attractors with different features. We perform a bifurcation analysis to determine and classify the dynamical structure of the system. Moreover, some of the dynamical regimes found, such as inhomogeneous steady states and inhomogeneous limit cycles can further be associated with artificial cell differentiation. We also report and characterize the emergence of chaotic dynamics resulting from the intercell coupling.

Quantized cycling time in artificial gene networks induced by noise and intercell communication.

We propose a mechanism for the quantized cycling time based on the interplay of cell-to-cell communication and stochasticity, by investigating a model of coupled genetic oscillators with known topology. In addition, we discuss how inhomogeneity can be used to enhance such quantizing effects, while the degree of variability obtained can be controlled using the noise intensity or adequate system parameters.

Multistability and clustering in a population of synthetic genetic oscillators via phase-repulsive cell-to-cell communication.

We show that phase-repulsive coupling eliminates oscillations in a population of synthetic genetic clocks. For this, we propose an experimentally feasible synthetic genetic network that contains phase repulsively coupled repressilators with broken temporal symmetry. As the coupling strength increases, silencing of oscillations is found to occur via the appearance of an inhomogeneous limit cycle, followed by oscillation death. Two types of oscillation death are observed: For lower couplings, the cells cluster in one of two stationary states of protein expression; for larger couplings, all cells end up in a single (stationary) cellular state. Several multistable regimes are observed along this route to oscillation death.

HIV-1 integrase complexes with DNA dissociate in the presence of short oligonucleotides conjugated to acridine.

The human immunodeficiency virus type 1 (HIV-1) integrase is an essential enzyme in the life cycle of the virus and is therefore an attractive target for the development of new antiviral drugs. Among them, inhibitors which are capable of targeting the preassembled integrase/DNA complex are of particular interest, because they could suppress integrase activity in the context of the HIV-1 preintegration complex. Here, we study the mechanism of action of 11-mer oligonucleotides, which are efficient inhibitors of the catalytic activity of integrase, provided that they are conjugated to a hydrophobic compound, acridine. To understand the mechanism of the conjugate inhibitory action, we used a steady-state fluorescence anisotropy assay, which allowed us to study the stability of the integrase/DNA complex in various conditions. We found that oligonucleotide-acridine conjugates induced the efficient dissociation of preassembled integrase/DNA complexes. The simultaneous presence of both acridine and an oligonucleotidic moiety is required for the inhibitory activity of conjugates. However, the dissociation effect is not dependent on the oligonucleotide sequence. Finally, our results suggest that the conjugates bind directly to integrase within its complex with DNA at a site different from the viral DNA binding site.