Bioinformatics teaching and extra science citations? 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.
Every cell division in budding yeast is inherently asymmetric and counts on the correct positioning of the mitotic spindle along the mother-daughter polarity axis for faithful chromosome segregation. A surveillance mechanism named the spindle position checkpoint (SPOC), monitors the orientation of the mitotic spindle and prevents cells from exiting mitosis when the spindle fails to align along the mother-daughter axis. SPOC is essential for maintenance of ploidy in budding yeast and similar mechanisms might exist in higher eukaryotes to ensure faithful asymmetric cell division. Here, we review the current model of SPOC activation and highlight the importance of protein localization and phosphorylation for SPOC function. See extra information at Inner kinetochore structure with Bashar Ibrahim.
For successful mitosis, metaphase has to be arrested until all centromeres are properly attached. The onset of anaphase, which is initiated by activating the APC, is controlled by the spindle assembly checkpoint MSAC. Mad2, which is a constitutive member of the MSAC, is supposed to inhibit the activity of the APC by sequestering away its co-activator Cdc20. Mad1 recruits Mad2 to unattached kinetochores and is compulsory for the establishment of the Mad2 and Cdc20 complexes. Recently, based on results from in vivo and in vitro studies, two biochemical models were proposed: the Template and the Exchange model. Here, we derive a mathematical description to compare the dynamical behaviour of the two models. Our simulation analysis supports the Template model. Using experimentally determined values for the model parameters, the Cdc20 concentration is reduced down to only about half.