Genetics Society of America (GSA)

Human fungal pathogens cause more than 1.5 million deaths annually. This burden is expected to grow as the immunocompromised population expands and as climate change promotes fungal adaptation to growth at human body temperatures. In particular, Cryptococcus species are responsible for life threatening meningitis and kill nearly 200,000 people a year. There are only three classes of effective antifungal drugs available to treat Cryptococcus and developing new drugs is difficult because many potential antifungal drugs are also toxic to humans. Effective use of this small set of drugs and development of new or complementary drugs will be aided by a better understanding of the genetic basis of both virulence and drug resistance.

My lab will utilize high-throughput genetic/genomic approaches to identify interesting drug resistance and susceptibility relevant pathways and follow up on those discoveries with targeted molecular biology analyses. In combination, these approaches enable powerful genome-wide interrogation of phenotypes of interest. We developed a transposon mutagenesis approach for Cryptococcus that uses massively parallel in vivo transposition coupled with targeted high-throughput sequencing (TN-seq) to determine how every gene affects growth in a given condition in a single experiment. This assay allows me to rapidly determine the genes required for resistance and susceptibility to an antifungal agent in Cryptococcus neoformans. More broadly, TN-seq will allow my research group to interrogate evolution of virulence across the Cryptococcus pathogenic species complex, including avirulent sister species.

Billmyre RB, Eickbush MT, Craig CJ, Lange JL, Wood C, Helston RM, Zanders SE (2022). Genome-wide identification of sexual-reproduction genes in fission yeast via transposon-insertion sequencing. In press at PLOS Genetics

Billmyre RB, Eickbush MT, Craig CJ, Lange JL, Wood C, Helston RM, Zanders SE (2022). Genome-wide identification of sexual-reproduction genes in fission yeast via transposon-insertion sequencing. In press at PLOS Genetics

Billmyre RB, Clancey SA, Li L, Doering T, Heitman J (2020). 5-fluorocytosine resistance is associated with hypermutation and alterations in capsule biosynthesis in Cryptococcus. Nature Communications. 11(127).

Billmyre RB, Clancey SA, Heitman J (2017). Natural mismatch repair mutations mediate phenotypic diversity and drug resistance in Cryptococcus deuterogattii. eLife, 6, e28802.

https://scholar.google.com/citations?user=jmFOfdQAAAAJ&hl=en