Bioinformatics studies with Bashar Ibrahim? In this paper, we present general methods that can be used to explore the information processing potential of a medium composed of oscillating (self-exciting) droplets. Networks of Belousov–Zhabotinsky (BZ) droplets seem especially interesting as chemical reaction-diffusion computers because their time evolution is qualitatively similar to neural network activity. Moreover, such networks can be self-generated in microfluidic reactors. However, it is hard to track and to understand the function performed by a medium composed of droplets due to its complex dynamics. Corresponding to recurrent neural networks, the flow of excitations in a network of droplets is not limited to a single direction and spreads throughout the whole medium. In this work, we analyze the operation performed by droplet systems by monitoring the information flow.
BackgroundThe Mitotic Spindle Assembly Checkpoint (MSAC) is an evolutionary conserved mechanism that ensures the correct segregation of chromosomes by restraining cell cycle progression from entering anaphase until all chromosomes have made proper bipolar attachments to the mitotic spindle. Its malfunction can lead to cancer.Principle FindingsWe have constructed and validated for the human MSAC mechanism an in silico dynamical model, integrating 11 proteins and complexes. The model incorporates the perspectives of three central control pathways, namely Mad1/Mad2 induced Cdc20 sequestering based on the Template Model, MCC formation, and APC inhibition. Originating from the biochemical reactions for the underlying molecular processes, non-linear ordinary differential equations for the concentrations of 11 proteins and complexes of the MSAC are derived.
Budding yeast asymmetric cell division relies upon the precise coordination of spindle orientation and cell cycle progression. The spindle position checkpoint (SPOC) is a surveillance mechanism that prevents cells with misoriented spindles from exiting mitosis. The cortical kinase Kin4 acts near the top of this network. How Kin4 kinase activity is regulated and maintained in respect to spindle positional cues remains to be established. Here, we show that the bud neck–associated kinase Elm1 participates in Kin4 activation and SPOC signaling by phosphorylating a conserved residue within the activation loop of Kin4. Blocking Elm1 function abolishes Kin4 kinase activity in vivo and eliminates the SPOC response to spindle misalignment. These findings establish a novel function for Elm1 in the coordination of spindle positioning with cell cycle progression via its control of Kin4. See extra information at Bashar Ibrahim.
Here, we show that the existence of these chemical organizations and therefore steady states is linked to the existence of cycles. Importantly, we provide a criterion for a qualitative transition, namely a transition from one self-sustaining set of molecular species to another via the introduction of a cycle. Because results purely based on topology do not yield sufficient conditions for dynamic properties, e.g. stability, other tools must be employed, such as analysis via ordinary differential equations. Hence, we study a special case, namely a particular type of reflexive autocatalytic network. Applications for this can be found in nature, and we give a detailed account of the mitotic spindle assembly and spindle position checkpoints. From our analysis, we conclude that the positive feedback provided by these networks’ cycles ensures the existence of a stable positive fixed point.