Biology subjects

Rapala, J. R.

Publications and source records attributed to Rapala, J. R..

3 recordsLinked to original sources

bioRxiv2026

Defining the Candidozyma auris pan-genome and essentiality

Candidozyma auris is a multi-drug resistant fungal pathogen that causes hospital outbreaks, but genetic variation and gene function in this organism remain undercharacterized. Here, we performed pangenome analysis on 695 genetically representative isolates of C. auris and found that only 2.6% of gene families varied in their presence, mainly consisting of gene loss events or clade-specific genes, highlighting the clonal nature of these strains. Using microbial genome-wide association, we identified two loci associated with altered keratinocyte adherence, including genes with unknown function. To look broadly at gene function, we developed a genome-scale insertional mutagenesis approach and identified 614 high-confidence essential genes. Nearly one-third of these genes exhibited divergent essentiality compared to the model yeasts Candida albicans and Saccharomyces cerevisiae. Together, this study highlights organism-specific biology and provides a comprehensive resource for identifying species-specific determinants of virulence and targets for antifungal drug development.

microbiology↗

bioRxiv2025

Deep homology and design of proteasome chaperone proteins in Candida auris

A central tenet of biology is that protein structure mediates the sequence-function relationship. Recently, there has been excitement about the promise of advances in protein structure modeling to generate hypotheses about sequence-structure-function relationships based on successes with controlled benchmarks. Here, we leverage structural similarity to identify rapidly evolving proteasome assembly chaperones and characterize their function in the emerging fungal pathogen Candida auris. Despite the large sequence divergence, we demonstrate conservation of structure and function across hundreds of millions of years of evolution, representing a case of rapid neutral evolution. Using the functional constraints on structure from these naturally evolved sequences, we prospectively designed de novo chaperones and demonstrate that these artificial proteins can rescue complex biological processes in the context of the whole cell.

evolutionary biology↗

bioRxiv2023

CryptoCEN: A Co-Expression Network for Cryptococcus neoformans reveals novel proteins involved in DNA damage repair

Elucidating gene function is a major goal in biology, especially among non-model organisms. However, doing so is complicated by the fact that molecular conservation does not always mirror functional conservation, and that complex relationships among genes are responsible for encoding pathways and higher-order biological processes. Co-expression, a promising approach for predicting gene function, relies on the general principal that genes with similar expression patterns across multiple conditions will likely be involved in the same biological process. For Cryptococcus neoformans, a prevalent human fungal pathogen greatly diverged from model yeasts, approximately 60% of the predicted genes in the genome lack functional annotations. Here, we leveraged a large amount of publicly available transcriptomic data to generate a C. neoformans Co-Expression Network (CryptoCEN), successfully recapitulating known protein networks, predicting gene function, and enabling insights into the principles influencing co-expression. With 100% predictive accuracy, we used CryptoCEN to identify 13 new DNA damage response genes, underscoring the utility of guilt-by-association for determining gene function. Overall, co-expression is a powerful tool for uncovering gene function, and decreases the experimental tests needed to identify functions for currently under-annotated genes.

genetics↗