The combined action of small molecules called hormones and the receptors that bind hormones to decipher their message allows organs to develop and grow in step with one another. During development of the model organism Drosophila melanogaster, pulses of the steriod hormone, ecdysone, cause tissue-specific developmental decisions to be made and also help to coordinate development of distant tissues and organs. Ecdysone binds the Ecdysone Receptor (EcR), a specialized transcription factor called a Type-II nuclear hormone receptor. The binding of ecydsone along with protein:protein interactions between EcR and coregulator proteins direct EcR to turn on or turn off genes. The Wardwell-Ozgo lab uses Drosophila to explore how coregulators inform steroid hormone signaling to direct tissue-specific developmental decisions. We achieve this by exploiting our innovative research platform which allows us to elegantly remove hormone signaling from individual cells and measure the resulting consequences.
We use our novel hormone disrupting tools and take genetic, molecular, and biochemical approaches to:
1) Probe biological phenomena
The transition from a reproductively immature stage through an intermediate stage to become a mature, reproductive adult is conserved in many metazoan species. Like humans, flies go through puberty! In the fruit fly this intermediate stage, analogous to human puberty, corresponds to the pupal transition between a juvenile larval period of growth and the reproductive adult stage. In both humans and Drosophila, this process is controlled by the relationship between internal cues from steroid hormone signaling the integration of external signals from the environment. One of the crucial environmental regulators of this transition is nutritional status. Poor nutritional status delays puberty in humans and pupariation in Drosophila, demonstrating that adequate nutrition is a conserved constraint for the juvenile-to-adult developmental transition. Little is known at the basic and molecular level about the intersection between the endocrine and environmental regulation of puberty. We take a discovery-based and modern genetic approach to explore how these pathways converge to regulate the pubertal transition.
2) Parse the moleclar genetics of nuclear hormone transcriptional regulation
Ecdysone controls devleopmental changes in multiple tissues that result in irreversible changes. However a longstanding, unanswered biological question is how tissues respond to the same hormone differently. The lab is interested in how coregulators in different tissues and at different times shape the way tissues respond to ecydsone pulses. We are generating a collection of genetic tools that allow us to disrupt specific coregulator:EcR interactions to determine their importance.