Tell us about an observation that sent your research in an unexpected direction.

Research doesn’t always follow a set path. Sometimes a single observation will send experiments on an entirely new course. Here, four scientists reveal pivotal moments in their scientific careers.

Martin Cohn

University of Florida

When investigating why limb development is arrested in python embryos, I was struck by the limb-like appearance of their genitalia. Wondering whether limb and genital development might involve similar processes, I decided to look into the mechanisms that build these appendages. I learned that, though defects in external genitalia are common in humans, almost nothing was known about the molecular processes involved. So my first graduate student compared gene expression in the limb and genital buds of mouse embryos, which are, thankfully, more tractable than pythons! Today, genital development is a major focus of my lab.

Elaine Fuchs

The Rockefeller University

In the 1990s, my lab was studying a skin protein that we thought reinforced adhesion between the epidermis and underlying dermis. We created a knockout mouse that showed mild skin blistering, but as the mice grew, they began twisting and writhing, and soon their sensory nervous systems had degenerated. We discovered that the affected gene had both epidermal and neuronal promoters, encoding different forms of protein. As expected, the epidermal form strengthened the internal framework and adherent properties of the epidermis. The neural form, on the other hand, stabilized the nerve cells and helped with long-distance protein trafficking. This work shaped our current interests in how stem cells use the cytoskeleton to build and repair tissues.

David L. Stern

Janelia Farm Research Campus

I like to make bold predictions about experimental outcomes and a running joke in my lab is that I’m almost always wrong. Most of our significant observations have taken our work in unanticipated directions. For example, our observations that certain body parts in fruit flies evolved entirely through changes in gene transcription led us into the field of cis-regulatory evolution. We had no desire to enter the quagmire of transcriptional regulation; we were forced into it by the data! As we dug deeper, we were surprised by the complexity and redundancy of these regulatory regions. This led us to new ways to tease apart the contributions of single nucleotide changes to morphological evolution, and new ways of thinking about how cis-regulatory regions function.

Luísa M. Figueiredo

Institute of Molecular Medicine, Lisbon, Portugal

As a postdoc, I showed that the enzyme DOT1B helps determine which glycoproteins appear on the surface of trypanosome parasites—protozoa that cause human disease. Trypanosomes have about 2,000 copies of the variant surface glycoprotein (VSG) gene, but only one is active at any given time. Because DOT1B adds methyl groups to the H3 histone—a nuclear protein that helps pack DNA into chromatin—I looked to see if the active VSG had more histone methyl groups than the silent VSGs. To my surprise, there were no histones on the active gene! This contradicted previous findings and led our research in a new direction: characterizing active VSG chromatin.

Photos: Cohn: Sarah Kiewel / University of Florida, Fuchs: Peter Ross, Stern: Matt Staley, Figueiredo: Kevin Wolf

Scientist Profile

The Rockefeller University
Cell Biology, Developmental Biology
Janelia Senior Group Leader
Janelia Research Campus
Experimental Evolutionary Biology, Genetics