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Lemieux, P.

Publications and source records attributed to Lemieux, P..

2 recordsLinked to original sources

Exit of spore dormancy transforms the yeast cytoplasm and the solubility of its proteome

The biophysical properties of the cytoplasm are major determinants of key cellular processes and adaptation. Many yeasts produce dormant spores that can withstand extreme conditions. We show that spores of Saccharomyces cerevisiae exhibit extraordinary biophysical properties, including a highly viscous and acidic cytosol. These conditions alter the solubility of more than 100 proteins such as metabolic enzymes that become more soluble as spores transit to active cell proliferation upon nutrient repletion. A key regulator of this transition is the heat shock protein Hsp42, which shows transient solubilization and phosphorylation, and is essential for the transformation of the cytoplasm during germination. Germinating spores therefore return to growth through the dissolution of protein assemblies, orchestrated in part by Hsp42 activity. The modulation of spores molecular properties are likely key adaptive features of their exceptional survival capacities.

cell biology↗

Toeholder: a software for automated design and in silico validation of toehold riboswitches

Synthetic biology aims to engineer biological circuits, which often involve gene expression. A particularly promising group of regulatory elements are riboswitches because of their versatility with respect to their targets, but early synthetic designs were not as attractive because of a reduced dynamic range with respect to protein regulators. Only recently, the creation of toehold switches helped overcome this obstacle by also providing an unprecedented degree of orthogonality. However, a lack of automated design and optimization tools prevents the widespread and effective use of toehold switches in high throughput experiments. To address this, we developed Toeholder, a comprehensive open-source software for toehold design and in silico comparison. Toeholder takes into consideration sequence constraints from experimentally tested switches, as well as data derived from molecular dynamics simulations of a toehold switch. We describe the software and its in silico validation results, as well as its potential applications and impacts on the management and design of toehold switches.

bioinformatics↗