Alexandre K. Dubé

The paper uses deep mutational scanning to analyze resistance mutations in Fks1, revealing distinct resistance landscapes for echinocandins and triterpenoids, including a novel triterpenoid-specific hotspot.

This study shows that gene duplication can lead to non-optimal expression levels that still confer a fitness advantage in yeast.

The paper identifies that peptide hydrophobicity affects their availability in yeast cells, impacting synthetic interaction strength beyond in vitro measurements.

This paper develops a heterologous expression system in yeast to rapidly test and discover resistance-conferring mutations from multiple pathogenic fungi.

The study shows that regulatory mutations cannot drive adaptation to 5-FC in yeast due to the flat fitness function around wild-type expression levels.

The paper shows that resistance mutations to antifungal drugs are conserved across fungal species but epistasis limits their transferability.

This paper trains a machine learning model to predict antifolate resistance mutations in Pneumocystis jirovecii using experimental data and computational modeling, finding mutations that confer resistance to trimethoprim-sulfamethoxazole.

The paper identifies key residues in Fks hotspots that confer echinocandin resistance in Saccharomyces cerevisiae using molecular dynamics and deep-mutational scanning.

The paper introduces a protein-fragment complementation assay to evaluate scaffold efficiency in yeast and identifies key factors affecting it.

The paper measures how mutations in residues near an SH3-binding motif affect binding strength in vivo and proposes a model involving interactions outside the canonical binding pocket.

The paper shows that paralog interference enhances negative selection on loss-of-function mutations, preserving genetic redundancy over longer timescales.

The paper presents a cost-effective method for constructing barcoded libraries for genes of any length using low-cost DNA synthesis and standard cloning technologies.

The paper shows that mutations in protein binding domains, combined with regulatory divergence, determine the fate of gene duplicates in a protein interaction network.

The paper evaluates 4,000 Erg11 variants to determine azole resistance and fitness costs, finding 33% resistance, 88% cross-resistance, and minimal fitness cost.

The paper quantifies the fitness cost of spurious phosphorylation in yeast by expressing tyrosine kinases and analyzing phosphoproteomes, finding a strong correlation between spurious phosphorylation and decreased growth.

The paper duplicates and evolves an homodimeric enzyme to show that compensatory mutations can lead to functional heteromers through subfunctionalization.

The paper identifies 355 resistance mutations in P. jirovecii DHFR to methotrexate using deep mutational scanning, revealing an allosteric mechanism at position F199.

The paper investigates the evolution of HRR25 ohnologs after a whole-genome duplication in yeast, finding that nonfunctionalization, not subfunctionalization, is the main trend.

This study identifies two distinct pathways for resistance to the antifungal 5-FC in yeast, showing that ecological factors influence which resistance mechanisms dominate.

BFG-PCA is a high-throughput method for discovering binary protein interactions using DHFR-PCA, showing high sensitivity and specificity across human and yeast protein pairs.

The paper shows that SH3 domain specificity in PPIs is influenced by host protein identity and domain position, not just intrinsic domain properties.

This study uses base editing to systematically mutate over 17,000 sites across 1,500 genes in yeast, identifying 1,100 sites affecting fitness and providing guidelines for effective gRNA design.

This paper develops a double selection strategy to improve CRISPR-Cas9 and base editing efficiency in yeast, enabling high-throughput mutagenesis screens.