Single-cell study links metabolism with nutrient signaling and reveals sources of variability.

Background: The yeast AMPK/SNF1 pathway is best known for its role in glucose de/repression. When glucose becomes limited, the Snf1 kinase is activated and phosphorylates the transcriptional repressor Mig1, which is then exported from the nucleus. The exact mechanism how the Snf1-Mig1 pathway is regulated is not entirely elucidated.

Network reconstruction and validation of the Snf1/AMPK pathway in baker's yeast based on a comprehensive literature review.

Background/objectives: The SNF1/AMPK protein kinase has a central role in energy homeostasis in eukaryotic cells. It is activated by energy depletion and stimulates processes leading to the production of ATP while it downregulates ATP-consuming processes. The yeast SNF1 complex is best known for its role in glucose derepression.

A Nonlinear Mixed Effects Approach for Modeling the Cell-To-Cell Variability of Mig1 Dynamics in Yeast.

The last decade has seen a rapid development of experimental techniques that allow data collection from individual cells. These techniques have enabled the discovery and characterization of variability within a population of genetically identical cells. Nonlinear mixed effects (NLME) modeling is an established framework for studying variability between individuals in a population, frequently used in pharmacokinetics and pharmacodynamics, but its potential for studies of cell-to-cell variability in molecular cell biology is yet to be exploited.

The mammalian AMP-activated protein kinase complex mediates glucose regulation of gene expression in the yeast Saccharomyces cerevisiae.

The AMP-activated protein kinase (AMPK) controls energy homeostasis in eukaryotic cells. Here we expressed hetero-trimeric mammalian AMPK complexes in a Saccharomyces cerevisiae mutant lacking all five genes encoding yeast AMPK/SNF1 components. Certain mammalian complexes complemented the growth defect of the yeast mutant on non-fermentable carbon sources.

Yeast AMP-activated protein kinase monitors glucose concentration changes and absolute glucose levels.

Analysis of the time-dependent behavior of a signaling system can provide insight into its dynamic properties. We employed the nucleocytoplasmic shuttling of the transcriptional repressor Mig1 as readout to characterize Snf1-Mig1 dynamics in single yeast cells. Mig1 binds to promoters of target genes and mediates glucose repression.

Potent anti-respiratory syncytial virus activity of a cholestanol-sulfated tetrasaccharide conjugate.

A number of different viruses including respiratory syncytial virus (RSV) initiate infection of cells by binding to cell surface glycosaminoglycans and sulfated oligo- and polysaccharide mimetics of these receptors exhibit potent antiviral activity in cultured cells. We investigated whether the introduction of different lipophilic groups to the reducing end of sulfated oligosaccharides would modulate their anti-RSV activity. Our results demonstrate that the cholestanol-conjugated tetrasaccharide (PG545) exhibited ∼5- to 16-fold enhanced anti-RSV activity in cultured cells compared with unmodified sulfated oligosaccharides.