Model-driven mapping of transcriptional networks reveals the circuitry and dynamics of virulence regulation

Key steps in understanding a biological process include identifying genes that are involved and determining how they are regulated. We developed a novel method for identifying transcription factors (TFs) involved in a specific process and used it to map regulation of the key virulence factor of a deadly fungus—its capsule. The map, built from expression profiles of 41 TF mutants, includes 20 TFs not previously known to regulate virulence attributes. It also reveals a hierarchy comprising executive, midlevel, and “foreman” TFs. When grouped by temporal expression pattern, these TFs explain much of the transcriptional dynamics of capsule induction. Phenotypic analysis of TF deletion mutants revealed complex relationships among virulence factors and virulence in mice. These resources and analyses provide the first integrated, systems-level view of capsule regulation and biosynthesis. Our methods dramatically improve the efficiency with which transcriptional networks can be analyzed, making genomic approaches accessible to laboratories focused on specific physiological processes

Characterizing the Role of Five Putative Capsule Regulating Genes in Cryptococcus neoformans

Mentor: Tamara L. Doering From the Washington University Undergraduate Research Digest: WUURD, Volume 7, Issue 2, Spring 2012. Published by the Office of Undergraduate Research, Joy Zalis Kiefer Director of Undergraduate Research and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Editor

Characterizing the Role of Five Putative Capsule Regulating Genes in Cryptococcus neoformans

From the Washington University Senior Honors Thesis Abstracts (WUSHTA), Volume 4, Spring 2012. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research / Assistant Dean in the College of Arts & Sciences; E. Holly Tasker, Editor; Kristin Sobotka, Undergraduate Research Coordinator. Mentor: Tamara L. Doerin