Search bioRxiv⌕ Search

Biology subjects

Golan, O.

Publications and source records attributed to Golan, O..

2 recordsLinked to original sources

Overall biomass yield of multiple nutrient sources

Microorganisms utilize nutrients primarily to generate biomass and replicate. When a single nutrient source is available, the produced biomass increases linearly with the initial amount of the available nutrient. This linear trend can be predicted to high accuracy by "black box models" that consider growth as a single chemical reaction with nutrients as substrates and biomass as a product. Since natural environments typically feature multiple nutrients, we here quantify the effect of co-utilization of multiple nutrients on bacterial biomass production. First, we demonstrate a mutual effect between the metabolism of different nutrient sources where the ability to utilize one is affected by the other. Second, we show that for some nutrient combinations, the produced biomass is no longer linear to the initial amount of nutrients. These observations cannot be explained by the traditional "black box models", presumably because the metabolism of one nutrient affects another, which is not accounted for by these models. To capture these observations, we extent "black box models" to include catabolism, anabolism, and biosynthesis of biomass precursors and phenomenologically add a mutual effect between the metabolism of the nutrient sources. The expanded model qualitatively recaptures the experimental observations and, unexpectedly, predicts that the produced biomass is not only dependent on the combination of nutrient sources but also on their relative initial amounts. We validate this prediction experimentally by demonstrating how measurement of the produced biomass can be used to determine how each nutrient effects the metabolic processes of another.

microbiology↗

Enhancer architecture sensitizes cell specific responses to Notch gene dose via a bind and discard mechanism

Notch pathway haploinsufficiency can cause severe developmental syndromes with highly variable penetrance. Currently, we have a limited mechanistic understanding of phenotype variability due to gene dosage. Here, we show that inserting a single enhancer containing pioneer transcription factor sites coupled to Notch dimer sites can unexpectedly induce a subset of Drosophila Notch haploinsufficiency phenotypes in an animal with wild type Notch gene dose. Mechanistically, this enhancer couples Notch DNA binding to degradation in a Cdk8-dependent, transcription-independent manner. Using mathematical modeling combined with quantitative trait and expression analysis, we show that tissues requiring long duration Notch signals are more sensitive to perturbations in Notch degradation compared to tissues relying upon short duration processes. These findings support a novel \"bind and discard\" mechanism in which enhancers with specific binding sites promote rapid Notch turnover, reduce Notch-dependent transcription at other loci, and thereby sensitize tissues to gene dose based upon signal duration.

developmental biology↗