Validation of a model of the GAL regulatory system via robustness analysis of its bistability characteristics

In Saccharomyces cerevisiæ, structural bistability generates a bimodal expression of the galactose uptake genes (GAL) when exposed to low and high glucose concentrations. This indicates that yeast cells can decide between using either the limited amount of glucose or growing on galactose under changing environmental conditions. A crucial requirement for any plausible mechanistic model of this system is that it reproduces the robustness of the bistable response observed in vivo against inter-individual parametric variability and fluctuating environmental conditions

The cognitive cell: bacterial behavior reconsidered

Research on how bacteria adapt to changing environments underlies the contemporary biological understanding of signal transduction, and signal transduction provides the foundation of the information-processing approach that is the hallmark of the ‘cognitive revolution,’ which began in the mid-20th century. Yet cognitive scientists largely remain oblivious to research into microbial behavior that might provide insights into problems in their own domains, while microbiologists seem equally unaware of the potential importance of their work to understanding cognitive capacities in multicellular organisms, including vertebrates. Evidence in bacteria for capacities encompassed by the concept of cognition is reviewed. Parallels exist not only at the heuristic level of functional analogue, but also at the level of molecular mechanism, evolution and ecology, which is where fruitful cross-fertilization among disciplines might be found

Evolutionarily stable and fragile modules of yeast biochemical network

Gene and protein interaction networks have evolved to precisely specify cell fates and functions. Here, we analyse whether the architecture of these networks affects evolvability. We find evidence to suggest that in yeast these networks are mainly acyclic, and that evolutionary changes in these parts do not affect their global dynamic properties. In contrast, feedback loops strongly influence dynamic behaviour and are often evolutionarily conserved. Feedback loops are often found to reside in a clustered manner by means of coupling and nesting with each other in the molecular interaction network of yeast. In these clusters some feedback mechanisms are biologically vital for the operation of the module and some provide auxiliary functional assistance. We find that the biologically vital feedback mechanisms are highly conserved in both transcription regulation and protein interaction network of yeast. In particular, long feedback loops and oscillating modules in protein interaction networks are found to be biologically vital and hence highly conserved. These data suggest that biochemical networks evolve differentially depending on their structure with acyclic parts being permissive to evolution while cyclic parts tend to be conserved

Characterizing biological systems: quantitative methods for synthetic genetic circuits in plants and intracellular mechanics

2018 Summer.Includes bibliographical references.To view the abstract, please see the full text of the document

PTK7 signaling complexes in neural crest cell migration

Cell migration is an important process during embryonic development and is strongly regulated by external signals, both chemical and mechanical. Neural crest (NC) cells are highly migratory cells, which are ideal for analyzing cell migration due to their high similarities to cancer cells. NC cells are induced at the border region of the neural folds and migrate along the anterior-posterior axis through the embryo. The NC cells have the ability to penetrate mesenchymal and ectodermal tissue but do not penetrate other NC cells, regulated by a process called contact inhibition of locomotion (CIL). CIL describes the process in which cells change their migration direction after contact with another cell. The non-canonical Wnt pathway is important for this process. Upon activation of the non-canonical Wnt pathway, the Frizzled receptor recruits the cytoplasmic protein Dishevelled to the membrane. This leads to activation of small GTPases and reorganization of the actin cytoskeleton. The transmembrane protein PTK7 (protein tyrosine kinase 7) is an activator of the non-canonical Wnt signaling pathway and expressed in NC cells. This study shows that in migrating NC cells PTK7, mediated by its extracellular domain, accumulates at cell-cell contact sites. A loss of function of PTK7 in Xenopus leads to an inhibition of NC cell migration. However, the role of PTK7 signaling during NC cell migration remains to be analyzed. During this study it has been shown that PTK7 loss of function leads to alteration of NC cell morphology and thereby inhibition of NC cell migration. This NC cell migration defects can be rescued by overexpression of Dishevelled. In addition, a new interaction partner was identified. The Rho guanine nucleotide exchanging factor Trio interacts with PTK7, co-localizes with PTK7 in NC cells and an overexpression of Trio rescues PTK7 loss of function defects in NC cell migration. In summary, this work has provided further insight into the PTK7 signaling pathway during NC cell migration