Katherine A. Kohnen
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Animals build, organize, and maintain a diversity of cell types throughout development and adulthood. Cellular diversity results from the regulated expression of genes, where most genes are “pleiotropic” with expression occurring in several cell types and/or developmental stages. Cell type and developmental stage-specific patterns of expression are activated by cis-regulatory element (CRE) DNA sequences. In contrast to genes, CREs are generally assumed to function in a modular non-pleiotropic manner. Where each CRE activates expression in one cellular context, and gene pleiotropy arises from their regulation by multiple modular CREs. This assumption shapes the way CREs are thought to impact development, evolution, and genetic disease. However, the generality of CRE modularity has not been satisfactorily demonstrated, as it is difficult to test for CRE activity or inactivity in all cell types and developmental stages. The major goal of my Honor Thesis research is to test whether CREs tend to be modular or possess pleiotropic gene expression regulating activities. For any identified pleiotropic CRE, I will reveal how their multiple expression activities are encoded in DNA sequence. Specifically, I will investigate 13 Drosophila melanogaster CREs that each activate gene expression in the abdomen of this fruit fly species by reporter transgene assays. For these CREs, I will inspect for additional reporter transgene expressions in embryonic, larval, pupal, and adult cell types. For any identified pleiotropic CRE, I will subject it to a series of discrete mutations to see whether zero, one, or multiple expression activities are disrupted by the introduced mutations. These experiments will provide a novel test of the modularity hypothesis and provide insights into how expression patterns are encoded in CREs. The outcomes have broad implications in biology, notably on the roles of CREs in development, evolution, and genetic disease.
Tom M. Williams
Primary Advisor's Department
Stander Symposium project, College of Arts and Sciences
United Nations Sustainable Development Goals
Good Health and Well-Being
"Challenging Genetic Dogma: Testing Whether Modularity is a General Feature of the Switches that Control Animal Gene Use" (2021). Stander Symposium Projects. 2118.