This proposal aims to develop enhanced genetic analysis systems in the zygomycete fungus Mucor circinelloides. M. circinelloides is an opportunistic fungal pathogen that causes mucormycosis. The incidence of mucormycosis is increasing due to a rising number of immunocompromised individuals. M. circinelloides also serves as a model system to study light sensing and understand RNAi-mediated gene expression regulation. In addition, M. circinelloides is a candidate for biofuel production. However, the genetic analysis of this fungal system is limited due to 1) a limited number of markers for transformation and 2) inefficient transformation and low frequent homologous gene replacement. In the studies proposed within this document, we aim to enhance our ability for genetic analysis in this important fungal system by proposing three aims: 1) construction of a recyclable pyrG marker system and 2) enhancement of homologous recombination in gene disruptions.

Public Health Relevance

We propose to develop robust genetics systems in Mucor circinelloides, one of the causal agents of mucormycosis, which is recognized as an emerging fungal infectious disease. Infection most frequently involves patients with diabetes, AIDS, hematologic malignancies, hematopoietic stem cell/solid organ transplantation, or trauma. Zygomycetes within the order Mucorales are causal agents of mucormycosis. However, genetics and molecular biology in zygomycetes are less well developed compared with model and even other pathogenic fungi. Our proposed work will shed light and provide a novel forum in the molecular biology and genetics of the understudied pathogenic zygomycetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
1R03AI119617-01A1
Application #
9109242
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Duncan, Rory A
Project Start
2016-02-01
Project End
2018-01-31
Budget Start
2016-02-01
Budget End
2017-01-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Duke University
Department
Genetics
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Vellanki, Sandeep; Navarro-Mendoza, Maria Isabel; Garcia, Alexis et al. (2018) Mucor circinelloides: Growth, Maintenance, and Genetic Manipulation. Curr Protoc Microbiol 49:e53
Garcia, Alexis; Vellanki, Sandeep; Lee, Soo Chan (2018) Genetic tools for investigating Mucorales fungal pathogenesis. Curr Clin Microbiol Rep 5:173-180