Donald T Fox

Please visit www.foxlabduke.com

Research overview:
Genomic extremes in organ development and repair.

The genome provides the blueprint for life. To achieve specialized cell or tissue function, specific genome features can be altered or exploited in extreme ways. My research program focuses on two such extreme genome variations: polyploidy and codon usage bias (defined below). In multicellular organisms with specialized organ systems, the function and regulation of these two extreme genome variations remains largely mysterious. We established accessible models where these two extreme genome variations impact cell and tissue biology.

1) Polyploidy. In numerous tissues or whole organisms, one nucleus can contain tens to thousands of genomes. Such whole genome duplication, or polyploidy, massively alters the transcriptome, proteome, and metabolome. We are only just beginning to understand the purposes of polyploidy in three crucial settings: organ development, organ repair, and ectopic polyploidy that can contribute to disease. My laboratory established accessible models of these processes using Drosophila. Our goal is to uncover fundamental functions and distinguishing regulation of polyploidy.

2) Codon usage bias. The genetic code is redundant, with 61 codons encoding 20 amino acids. Despite this redundancy, synonymous codons encoding the same amino acid occur at varying frequencies. “Rare” codons occur least often while other “common” codons occur most often. Altering codon bias across evolution affects mRNA translation and has biological consequences. The impact of codon bias on tissue-specific differentiation has been largely unexplored. In Drosophila, we discovered that the ability to express genes enriched in rare codons is a defining characteristic of at least two specific organs. We are uncovering evidence that these organs express rare codon-enriched genes to achieve cell and tissue-specific identity. We are thus well-poised to define, for the first time, the role of codon bias in tissue-specific development.