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Uncovering molecular mechanisms that regulate mating in Histoplasma capsulatum

Laskowski, Meggan C.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1250166185

Abstract Details

2009, PhD, University of Cincinnati, Medicine : Pathobiology and Molecular Medicine.
Genetic techniques requiring recombination in the pathogenic fungus, Histoplasma capsulatum, are currently limited because the organism rapidly loses mating ability in culture. The studies presented in this body of work sought to determine molecular mechanisms that regulate mating in H. capsulatum, as a step toward preventing or reversing the loss of mating ability in cultured strains. Fungal mating loci are characterized by the presence of transcription factors that regulate mating, and some mating loci contain multiple genes involved in the mating response. We identified the mating locus of H. capsulatum and showed that the transcription factors MAT1-1-1 and MAT1-2-1, present at the MAT1-1 and MAT1-2 idiomorphs of the mating locus, respectively, are transcriptionally responsive to mating conditions. To identify additional components of mating regulation in H. capsulatum, we used syntenic analysis to identify a putative alpha pheromone. The alpha pheromone was found to be produced by MAT1-2 mating type organisms under mating conditions, and it was determined that organisms of MAT1-1 mating type respond to the alpha pheromone. UC1, an H. capsulatum strain that gained the ability to form empty cleistothecia with a mating partner after insertional mutagenesis, was used to determine additional molecular mechanisms that contribute to cleistothecia formation. Silencing HMK1, a predicted MAP kinase involved in the pheromone response MAP kinase pathway, had no effect on cleistothecia formation by UC1; however, Pkc1 activity was linked with pheromone production in this strain. These studies showed that the H. capsulatum mating locus transcription factors and the alpha pheromone play a role in mating, similar to that of other fungi. Pkc1 activity, however, is only indirectly linked to mating ability in other fungi, opening up areas for future studies determining the role Pkc1 plays in regulation of mating and mating competency in H. capsulatum.
George Smulian, MD (Committee Chair)
George Deepe, MD (Committee Member)
Judith Rhodes, PhD (Committee Member)
Jason Blackard, PhD (Committee Member)
Eric Gruestein, PhD (Committee Member)
165 p.
Biology
Histoplasma capsulatum; fungi; mating; pheromone; mating locus

Recommended Citations

Citations

  • Laskowski, M. C. (2009). Uncovering molecular mechanisms that regulate mating in Histoplasma capsulatum [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1250166185

    APA Style (7th edition)

  • Laskowski, Meggan. Uncovering molecular mechanisms that regulate mating in Histoplasma capsulatum. 2009. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1250166185.

    MLA Style (8th edition)

  • Laskowski, Meggan. "Uncovering molecular mechanisms that regulate mating in Histoplasma capsulatum." Doctoral dissertation, University of Cincinnati, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1250166185

    Chicago Manual of Style (17th edition)

ucin1250166185
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© 2009, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.