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|Title: ||Systematic Genetic Analysis of Dimorphism in Saccharomyces cerevisiae|
|Authors: ||Ryan, Owen W.|
|Advisor: ||Boone, Charles|
|Department: ||Molecular and Medical Genetics|
|Issue Date: ||11-Jan-2012|
|Abstract: ||Deletion mutant collections allow for the systematic study of gene function by linking a genotype to a phenotype. Furthermore, these collections permit the parallel and quantitative study of phenotypes, which is the foundation of functional genomics. I begin by summarizing the methods used and data derived from the field of functional genomics using the Baker’s yeast Saccharomyces cerevisiae, and provide important background information on the origins of the filamentous growth-competent S.cerevisiae strain Σ1278b, and the developmental process of fungal dimorphism.
I describe my efforts in creating a complete deletion mutant collection in the filamentous growth-competent S.cerevisiae strain Σ1278b, and the subsequent phenotypic analysis of that deletion mutant collection. By quantitatively measuring mutant phenotypes of cells undergoing haploid invasive growth, biofilm mat formation and diploid pseudohyphal growth, I studied the clinically relevant developmental process of fungal dimorphism. I present the first genome-wide and quantitative phenotypic analysis of fungal dimorphism and identify a novel transcription factor encoded by the open reading frame YDL233W, which I named FMR1for Filamentation Master Regulator 1. By performing genetic, cell biological, biochemical, and expression analysis, I demonstrate that Ydl233w acts by forming a protein complex with the DNA-binding transcription factors Flo8 and Mss11 and this complex binds to a specific element within the promoter of the surface adherence mediating gene FLO11.
I directly compare the essential gene sets between the Σ1278b deletion collection and the reference deletion collection made in the S288c genetic background completed by the Yeast Deletion Consortium in 2002. I find that most essential genes are shared between these two strains but a number of genes are essential for viability in only one genetic background, a phenomenon termed conditional essentiality. I describe the genetic basis of conditional essentiality as a consequence of the complex inheritance of background-specific alleles.
Lastly, I summarize the scientific advancements of my research using the Σ1278b deletion collection, and highlight some potential applications for both the data derived from my research and the deletion mutant collection itself. The Σ1278b deletion collection provides a valuable resource for yeast geneticists, evolutionary biologists, researchers of fungal disease, and researchers interested in modeling the genetics that underlie complex traits and diseases.|
|Appears in Collections:||Doctoral|
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