Molecular Biology, Plant Biology
Salk Institute for Biological Studies
Dr. Ecker is a Howard Hughes Medical Institute–Gordon and Betty Moore Foundation investigator. He is also a professor in the Plant Molecular and Cellular Biology Laboratory at the Salk Institute for Biological Studies.
Joseph Ecker is using Arabidopsis thaliana, mice, and human cells to study epigenetic processes. In particular, his laboratory studies epigenetic inheritance and the role of DNA methylation during normal development and disease states.
In a quiet abbey in the 1850s, Gregor Mendel grew thousands of pea plants, famously showing that traits can be inherited in predictable ways. Joseph Ecker, a Mendel of the modern age, is trying to figure out how plant genes work—but with the help of the fastest, most sophisticated technology available. "I don't have the patience of a monk," he says with a chuckle.
For nearly 25 years, Ecker has been at the forefront of research to decode the genome ofArabidopsis thaliana, a mustard weed that has become the gold standard of plant research. He was a leader of the international effort to sequence all of Arabidopsis's 25,000-odd genes, which was completed in 2000. More recently, Ecker has turned to deciphering the so-called epigenome, the layer of molecular tweaks that act on DNA to turn genes on and off. The genetic reference books developed by Ecker and his colleagues may have enormous practical uses in crop engineering. But his work is also showing that the complicated genetic underpinnings of plants and humans are more similar than anybody thought.
Ecker has been fascinated by plants since the age of three or four. Growing up in the coal country of central Pennsylvania, he spent his summers unearthing fern fossils from shale deposits. "It is really remarkable when you crack open a rock and find some image of plant life from millions of years back," he says.
He studied biology at The College of New Jersey and when he graduated, in 1978, he was eager to jump into the field's hottest area: visualizing, manipulating, and cloning DNA. For graduate school, he joined a research group at Pennsylvania State University College of Medicine that was using electron microscopy to uncover the molecular structure of the chickenpox virus genome. Ecker was pulled into plant research only after giving a journal club presentation about how Agrobacterium genes, like tumor viruses in animals, can jump into plant genomes.
When he began his postdoctoral fellowship in Ron Davis's lab at Stanford University, the lab dabbled in a host of plant models, including corn, peas, carrots, and zucchini. (New HHMI-GBMF investigator Jeff Dangl, one of his colleagues at the time, used to joke, "Are you guys doing science or making succotash?") But Ecker was impatient with how long it takes these species to breed: maize plants, for example, produce only two generations a year.
So, like many other young scientists at the time, Ecker turned to Arabidopsis. One plant can produce thousands of seeds, which mature in just six weeks. After its genome was sequenced, Ecker started making Arabidopsis mutants to better understand the function of individual genes. He has created some quarter-million mutants to date, all of which are openly available to the scientific community.
The cost of genomic sequencing has plummeted in the past few years. "The first time, it cost $70 million dollars to complete the Arabidopsis genome. Today, one time coverage of the genome is basically the price of a cup of Starbucks," he says. Taking advantage of lower costs, in 2008 Ecker helped launch the 1001 Genomes project, an effort to sequence 1,001 natural Arabidopsis strains worldwide, from the Arctic to Uzbekistan.
Advances in sequencing technology have also helped Ecker probe the epigenome in both plants and people. One of the most common kinds of epigenetic regulation happens when a bulky methyl group attaches to a particular DNA letter, effectively silencing the gene in that spot. In 2006, Ecker published the first genome-wide map of DNA methylation inArabidopsis. Three years later, he did the same thing for two kinds of human cells: embryonic stem cells and differentiated lung cells. Much to his surprise, he discovered that human stem cells show a pattern of methylation previously thought to happen only in plants.
"I have a tool-driven lab, so there's plant people and animal people working side by side," Ecker says. "You need different systems to address different questions. But in the end, I think the answer's going to come from the cross-over."