Computational Biology, Evolutionary Biology
University of California, Berkeley
Dr. Eisen is also a professor of genetics, genomics, and development in the Department of Molecular and Cell Biology and a professor of integrative biology at the University of California, Berkeley.
Function and Evolution of Transcriptional Enhancers
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.
HHMI Investigator Michael Eisen strives to ensure that advances made in his lab reach as broad an audience as possible, and to help other researchers do the same.
As a postdoctoral researcher in the lab of Patrick O. Brown, who was an HHMI investigator at Stanford University, Eisen developed software and techniques to analyze data from DNA microarrays – tools used in labs worldwide to simultaneously measure the activity of thousands of genes.
While tools that sift through mountains of microarray data are important, what Eisen and his lab mates really needed was more biological context for that data. “When you’re working on just one gene at a time, you can know everything there is to know about that gene,” he says. “But when you shift to studying the entire genome, you can only know a tiny fraction of the relevant information needed to interpret an experiment.”
Eisen and Brown thought that if all the research articles relevant to a particular microarray experiment were in a single online location, interpreting the results would be much easier. At the time, more and more scientific publishers were posting their articles online, but most were charging substantial fees for access. Eisen and Brown realized that scientists needed to change the way they publish their findings. “We slowly became convinced that we needed to create a new model of scientific publishing,” he says.
In 2001, Eisen, Brown, and Nobel Laureate Harold Varmus founded the Public Library of Science (PLoS), which now publishes seven online peer-reviewed scientific and medical journals. PLoS allows free, unrestricted use and distribution of the articles it publishes.
Launching PLoS did not divert Eisen from his research career. Since 2000, he has been a computational and evolutionary biologist, first at the Lawrence Berkeley National Laboratory and, since 2005, at the University of California, Berkeley. His lab uses fruit flies in the genus Drosophila to study how DNA sequences that determine when genes are turned on and off shape an animal’s form and behavior.
Realizing that patterns and principles are likely to emerge when scientists compare the genomes of related species, Eisen helped spur a major international effort to sequence the genomes of 12 species of Drosophila. His lab led the labor-intensive analysis of the data the project generated. Information from the 12 Genomes Project was published in 2007 and is a rich resource for fruit fly researchers.
The Eisen lab’s analyses of these genomes and those of other flies are helping reveal how genes are regulated in Drosophila embryos. “You can think of these genomes as experiments that evolution has already done for you,” he says.
The function of regulatory DNA in fruit flies may seem far removed from medical applications, but Eisen insists that there is an important link. “In just a few years, everyone will be able to know their own genome sequence. At that point, a great challenge is going to be understanding the consequences of genetic variation,” he says. “Our interest in the long run is to apply what we learn in Drosophila to understanding variation in the human genome.”