As the first round of rotations for the year comes to a close, we wanted to share that John Van Dusen from the Department of Microbiology has been working with Audra on the eukaryome work. Thanks for rotating with us, John!
John Van Dusen
Extracting and Purifying DNA from Oral Samples for the Eukaryome Project.
Loyola University Chicago, BS in Biology
Biofilms are organized communities of microbial cells that promote persistence among bacterial and fungal species. Biofilm formation by host-associated Candida species of fungi occurs on both tissue surfaces and implanted devices, contributing to host colonization and disease. In C. albicans, biofilms are built sequentially by adherence of yeast to a surface, invasion into the substrate, the formation of aerial hyphal projections, and the secretion of extracellular matrix. Measurement of these biofilm-related phenotypes remains highly qualitative and often subjective. Here, we designed an informatics pipeline for quantifying filamentation, adhesion, and invasion of Candida species on solid agar media and utilized this approach to determine the importance of these component phenotypes to C. albicans biofilm production. Characterization of 23 C. albicans clinical isolates across three media and two temperatures revealed a wide range of phenotypic responses among isolates in any single condition. Media profoundly altered all biofilm-related phenotypes among these isolates, whereas temperature minimally impacted these traits. Importantly, the extent of biofilm formation correlated significantly with the additive score for its component phenotypes under some conditions, experimentally linking the strength of each component to biofilm mass. In addition, the response of the genome reference strain, SC5314, across these conditions was an extreme outlier compared to all other strains, suggesting it may not be representative of the species. Taken together, development of a high-throughput, unbiased approach to quantifying Candida biofilm-related phenotypes linked variability in these phenotypes to biofilm production and can facilitate genetic dissection of these critical processes to pathogenesis in the host.
We are very excited to formally welcome Dr. Paula Sundstrom to the lab as she conducts her research here in the Riffe building as an Adjunct Professor. Her insight and research experience has already started driving new projects and ideas. Welcome Paula!
“I seek to address basic questions about interactions between Candida albicans and human hosts that enable commensal and pathogenic states. The approaches include experimental evolution, genomics, bioinformatics and murine animal models to understand processes such as C. albicans’ gene expression in the host, diversity and host immune responses that contribute to both protection and damage.”
Candida albicans commensal and pathogenic states. Experimental evolution, genomics, bioinformatics and murine animal models.
Pomona College, Claremont, CA (B.A.)
University of Washington, Seattle (Ph.D.)
While adapting to the new normal, we are very excited to share that Leah Anderson has been accepted into the University of Washington Genome Sciences program. We wish her best!
We welcome Anna Mackey into the lab as the new lab manager, working on identifying gut microbiome diversity, and Amber Anger from MCDB who will be rotating with a TLO based project.
Investigating gut microbiome diversity, specifically focusing on the eukaryome, along urbanization and industrialization gradients.
The Ohio State University, BS Mathematical Biology
Create KO strains for each of the TLO genes, examine the resulting mutant phenotypes, and use bioinformatics to characterize the TLO gene family.
University of Michigan, B.S. in Molecular Biology & Central Michigan, M.Sc. in Biochemistry, Cell, & Molecular Biology
Dr. Matthew Anderson was recently awarded 1R01AI148788-01A1 for the work entitled “Quantitative Genetics Approaches to Candida albicans Pathogenesis.”
Public health relevance:
Genetic variation contributes to the observable diversity in biological traits found within single species. High levels of genetic variation exist between strains of the most clinically relevant human fungal pathogen, Candida albicans, but the consequences of this variation on its ability to cause disease is significantly understudied. Understanding the genetic differences in C. albicans that lead to more or less severe clinical disease will help identify potential therapeutic targets to reduce the burden of C. albicans pathogenesis.
Matthew Dunn was recently awarded the 2020 AHA Predoctoral Fellowship for his project entitled: “Evolutionary outcomes of TLO gene family expansion in Candida albicans”
Genome instability often leads to cell death but can also give rise to innovative genotypic and phenotypic variation through mutation and structural rearrangements. Repetitive sequences and chromatin architecture in particular are critical modulators of recombination and mutability. In Candida albicans, four major classes of repeats exist in the genome: telomeres, subtelomeres, the major repeat sequence (MRS), and the ribosomal DNA (rDNA) locus. Characterization of these loci has revealed how their structure contributes to recombination and either promotes or restricts sequence evolution. The mechanisms of recombination that give rise to genome instability are known for some of these regions, whereas others are generally unexplored. More recent work has revealed additional repetitive elements, including expanded gene families and centromeric repeats that facilitate recombination and genetic innovation. Together, the repeats facilitate C. albicans evolution through construction of novel genotypes that underlie C. albicans adaptive potential and promote persistence across its human host.
Genes 2019, 10(11), 866; https://doi.org/10.3390/genes10110866
Meiosis is a conserved tenet of sexual reproduction in eukaryotes, yet this program is seemingly absent from many extant species. In the human fungal pathogen Candida albicans, mating of diploid cells generates tetraploid products that return to the diploid state via a non-meiotic process of depolyploidization known as concerted chromosome loss (CCL). Here, we report that recombination rates are more than three orders of magnitude higher during CCL than during normal mitotic growth. Furthermore, two conserved ‘meiosis-specific’ factors play central roles in CCL as SPO11 mediates DNA double-strand break formation while both SPO11 and REC8 regulate chromosome stability and promote inter-homolog recombination. Unexpectedly, SPO11 also promotes DNA repair and recombination during normal mitotic divisions. These results indicate that C. albicans CCL represents a ‘parameiosis’ that blurs the conventional boundaries between mitosis and meiosis. They also reveal parallels with depolyploidization in mammalian cells and provide potential insights into the evolution of meiosis.
As we fully enter the new semester we would like to acknowledge two undergraduates who have recently joined the Anderson Lab team. Shruti Gupta is working with Robert Fillinger investigating filamentation using quantitative genetics and Molly Rambeau is working with Audra Crouch studying the mycobiome in Native American populations. Welcome!
Identifying genes that regulate filamentation in Candida albicans using quantitative genetics. Using RNA-seq from human cells to identify the involved pathways.
Data Analytics major (Biomedical Informatics track), Molecular Genetics minor
Studying the mycobiome in native american populations and determining if shifts in mycobiome is a causation behind rheumatoid arthritis.
Pursuing B.S. in Biology (pre-med track)
Robert Fillinger was recently awarded Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31) for his project entitled: “Quantitative genetic approaches to Candida albicans oropharyngeal pathogenesis”
Here, quantitative trait loci (QTL) approaches are developed for parasexual species and applied to identification of genetic differences between Candida albicans strains governing differential abilities to filament or damage epithelial surfaces during oropharyngeal candidiasis and filamentation.