Cardiovascular disease (CVD) is an important contributor to morbidity and mortality in American Indian communities. The Strong Heart Study (SHS) was initiated in response to the need for population based estimates of cardiovascular disease in American Indians. This study demonstrates that MBL2 genotype associates with immune reactivity to C. pneumoniae in the SHS cohort. Thus, MBL2 may contribute to the progression of cardiovascular disease (CVD) among American Indians indirectly through pathogen interactions in addition to its previously defined roles.
Summary: Galleria mellonella serves as an invertebrate model for disseminated candidiasis. Here, we detail the infection protocol and provide supporting data for the model’s effectiveness.
Dunn, M. J., Woodruff, A. L., Anderson, M. Z. The Galleria mellonella Waxworm Infection Model for Disseminated Candidiasis. J. Vis. Exp. (141), e58914, doi:10.3791/58914 (2018).
We are excited to welcome Audra Crouch for the second rotation cycle this year! Audra comes from the Department of Microbiology and is rotating with the ongoing microbiome work in the lab.
Studying the mycobiome in native american populations and determining if shifts in mycobiome is a causation behind rheumatoid arthritis
Graduate Rotation Student
University of Lynchburg, BS Biomedical Science and Music Performance Minor
With the new academic year fully in motion we welcome Pranav Rana as a rotation student in the lab from the Department of Microbiology!
Investigating the role of TLO gene family expansion in C. albicans using CRISPR-mediated gene editing
Graduate Rotation Student
University of Idaho, B.S. Microbiology
Abstract: The opportunistic fungal pathogen Candida albicans lacks a conventional sexual program and is thought to evolve, at least primarily, through the clonal acquisition of genetic changes. Here, we performed an analysis of heterozygous diploid genomes from 21 clinical isolates to determine the natural evolutionary processes acting on the C. albicans genome. Mutation and recombination shaped the genomic landscape among the C. albicans isolates. Strain-specific single nucleotide polymorphisms (SNPs) and insertions/deletions (indels) clustered across the genome. Additionally, loss-of-heterozygosity (LOH) events contributed substantially to genotypic variation, with most long-tract LOH events extending to the ends of the chromosomes suggestive of repair via break-induced replication. Consistent with a model of inheritance by descent, most polymorphisms were shared between closely related strains.
However, some isolates contained highly mosaic genomes consistent with strains having experienced interclade recombination during their evolutionary history. A detailed examination of mitochondrial genomes also revealed clear examples of interclade recombination among sequenced strains. These analyses therefore establish that both (para)sexual recombination and mitotic mutational processes drive evolution of this important pathogen. To further facilitate the study of C. albicans genomes, we also introduce an online platform, SNPMap, to examine SNP patterns in sequenced isolates.
Abstract: Candida albicans surface-attached biofilms serve as a reservoir of cells to perpetuate and expand an infection; cells released from biofilms on catheters have direct access to the bloodstream. Biofilm dispersal yeast cells exhibit enhanced adhesion, invasion, and biofilm formation compared to their planktonic counterparts. Here, we show using transcriptome sequencing (RNA-seq) that dispersed yeast cells are developmentally distinct from the cells in their parent biofilms as well as from planktonic yeast cells.
Dispersal cells possess an anticipatory expression pattern that primes them to infect new sites in the host, to survive in nutrient-starved niches, and to invade new sites. These studies identified dispersal cells as a unique proliferative cell type of the biofilm and showed that they could serve as targets for antibiofilm drug development in the future.
Candida albicans Dispersed Cells Are Developmentally Distinct from Biofilm and Planktonic Cells
Priya Uppuluri, Maikel Acosta Zaldívar, Matthew Z. Anderson, Matthew J. Dunn, Judith Berman, Jose Luis Lopez Ribot, Julia R. Köhler
mBio Aug 2018, 9 (4) e01338-18; DOI: 10.1128/mBio.01338-18
As we enter the middle of summer we are very excited to welcome Leah Anderson as the new lab technician for the Anderson Lab! Leah will be continuing work conducted previously by Pamela Washington. Welcome Leah!
Investigating the role of macrophage caspases in defending against Candida infections.
B.S. Molecular Genetics, B.M. Violin Performance
Recent scientific developments have drawn renewed attention to the complex relationships among Indigenous peoples, the scientific community, settler colonial governments, and ancient human remains. Increasingly, DNA testing of ancestral remains uncovered in the America s is being used in disputes over these remains. However, articulations of ethical principles and practices in paleogenomics have not kept pace, even as results of these studies can have negative consequences, undermining or complicating community claims in treaty, repatriation, territorial, or other legal cases. Paleogenomic narratives may also misconstrue or contradict community histories, potentially harming community or individual identities. Paleogenomic data can reveal information about descendant communities that may be stigmatizing, such as genetic susceptibilities to disease. Given the potential consequences for Indigenous communities, it is critical that paleogenomic researchers consider their ethical obligations more carefully than in the past.
Jessica Bardill, Alyssa C. Bader, Nanibaa’ A. Garrison, Deborah A. Bolnick, Jennifer A. Raff, Alexa Walker, Ripan S. Malhi, the Summer internship for INdigenous peoples in Genomics (SING) Consortium
Science 27 Apr 2018:
Vol. 360, Issue 6387, pp. 384-385
As the temperatures rise in sunny Columbus, Ohio, we welcome rotation student Kyle Spencer and summer student Cameron Ramos. Kyle joins us from the BSGP program on his summer rotation and Cameron joins us from the BREIS program. Welcome to both of you!
Exploration of Candida albicans interactions with macrophages for host immunity.
Graduate Rotation Student
Central Michigan University, MS, Molecular Biology, BS, Biomedical Science
The Role of the Fungal Microbiome in Rheumatoid Arthritis among Native Americans.
Environmental Studies and Native American Indigenous Studies
Gene duplication is a rapid mechanism to generate additional sequences for natural selection to act upon and confer greater organismal fitness. If additional copies of the gene are beneficial, this process may be repeated to produce an expanded gene family containing many copies of related sequences. Following duplication, individual gene family members may retain functions of the ancestral gene or acquire new functions through mutation. How functional diversification accompanies expansion into large gene families remains largely unexplored due to the difficulty in assessing individual genes in the presence of the remaining family members. Here, we addressed this question using an inducible promoter to regulate expression of individual genes of the TLO gene family in the commensal yeast and opportunistic pathogen Candida albicans, which encode components of a major transcriptional regulator. Induced expression of individual TLOs affected a wide range of phenotypes such that significant functional overlap occurred among TLO genes and most phenotypes were affected by more than one TLO. Induced expression of individual TLOs did not produce massive phenotypic effects in most cases, suggesting that functional overlap among TLO genes may buffer new mutations that arise. Specific sequence variants among the TLO genes correlated with certain phenotypes and these variants did not necessarily correlate with sequence similarity across the gene. Therefore, individual TLO family members evolved specific functional roles following duplication that likely reflect a combination of inherited function and new mutation.
Dunn, M.J., Kinney, G.M., Washington, P.M., Berman, J., Anderson, M.Z. Functional diversification accompanies gene family expansion of MED2 homologs in Candida albicans. PLoS Genet 14(4): e1007326. https://doi.org/10.1371/journal.pgen.1007326