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Nijhout, F.

Publications and source records attributed to Nijhout, F..

2 recordsLinked to original sources

TGF-beta/Activin ligand Myoglianin couples muscle growth to the initiation of metamorphosis

Although the mechanisms that control growth are now well understood, the mechanism by which animals assess their body size remains one of the great puzzles in biology. The final larval instar of holometabolous insects, after which growth stops and metamorphosis begins, is specified by a threshold size. We investigated the mechanism of threshold size assessment in the tobacco hornworm, Manduca sexta. The threshold size was found to change depending on the amount of exposure to poor nutrient conditions whereas hypoxia treatment consistently led to a lower threshold size. Under these various conditions, the mass of the muscles plus integuments was correlated with the threshold size. Furthermore, the expression of myoglianin (myo) increased at the threshold size in both M. sexta and Tribolium castaneum. Knockdown of myo in T. castaneum led to larvae that underwent supernumerary larval molts and stayed in the larval stage permanently even after passing the threshold size. We propose that increasing levels of Myo produced by the growing tissues allow larvae to assess their body size and trigger metamorphosis at the threshold size.

developmental biology↗

Drug target discovery via network modeling: a mathematical model of the E. coli folate network response to trimethoprim

The antibiotic trimethoprim targets the bacterial dihydrofolate reductase enzyme and subsequently affects the entire folate network. We present an expanded mathematical model of trimethoprims action on the Escherichia coli folate network that greatly improves upon Kwon et al. (2008). The improvement upon the Kwon Model lends greater insight into the effects of trimethoprim at higher resolution and accuracy. More importantly, the presented mathematical model enables drug target discovery in a way the earlier model could not. Using the improved mathematical model as a scaffold, we use parameter optimization to search for new drug targets that replicate the effect of trimethoprim. We present the model and model-scaffold strategy as an efficient route for drug target discovery.

systems biology↗