During early development in animals, thousands of cellular cues governing the expression of genes transform a mass of undifferentiated cells into a discernible embryo. This collection of proteins and DNA fragments regulates embryogenesis by activating genes at the right place and time, generating a body plan for the embryo. Michael Eisen is particularly interested in a subset of these regulatory elements called transcriptional enhancers – relatively short snippets of noncoding DNA that boost gene expression.
Using Drosophila as a model organism, Eisen’s lab team investigates the role of enhancers in cellular development and body plan layout. Once bound by proteins known as transcription factors, enhancers initiate transcription of particular genes. Several years ago, Eisen’s team discovered that in fruit flies, virtually all enhancers activated in early development have a short sequence of DNA in common – CAGGTAG – a sequence that turns out to be the docking site for a new transcription factor protein called Zelda. The team showed that Zelda binds to DNA sequences destined to be enhancers, kicking off a cascade of events that biochemically flags the sequence as a future enhancer.
In other projects, Eisen’s lab team focuses on how microbial populations can biochemically coerce a host animal into behaving favorably for the microorganisms’ survival. For example, the Entomophthora fungus has evolved the ability to infiltrate and chemically commandeer a fruit fly, forcing it to climb to an elevated area where it then dies and disperses fungal spores. Eisen’s team is also pursuing the connection between gut bacteria and animal behavior, manipulating the microflora in Drosophila and monitoring the impact on fly behavior and on small molecules produced by the bacteria. By identifying potential nervous system targets for these small molecules, the scientists aim to piece together how the microbes influence animal behavior.
All of my Michael Eisen's research is supported by HHMI. Current members of his laboratory are supported by fellowships from the National Institutes of Health, the National Science Foundation, and the American Cancer Society.