For Associate Professor of Biology Lori Eggert, collaboration is at the heart of everything she does. From local to international projects, and even within her lab, collaboration is invaluable. Dr. Eggert’s life and research are a testament to the amazing feats that can be accomplished with coordinated, hard work from many different, devoted sources.
Doing maize genetics, according to one geneticist, is “really cool.” It is exactly this kind of enthusiasm that fuels Karen Cone, Professor of Biological Sciences at MU, who specializes in plant genetics. Asked to summarize what researchers in her field actually do, Cone laughs and responds, “Geneticists make mutants…a geneticist learns about the way something works in real life by screwing it up, trying to figure out what’s wrong with the mutant, and then inferring what is normal when the mutant isn’t there.” The mutants that Cone makes involve corn and purple pigmentation.
Dr. Eggert talks about the basics of the work she does, including noninvasive sampling and DNA extraction from those hard samples. She provides some expertly simplified explanations of these complex procedures.
With the kind of scale that Dr. Eggert’s projects involve, collaboration is essential. Here she describes some of those collaborations and how they work.
Zaghouani’s passion for immunology springs from a love of genetics and a fascination with the human immune system. He sees his work as more a hobby than a job, and has been able to share his knowledge of the subject with his many graduate students and lab technicians.
Cone responds to some basic questions about doing genetics research with plants, discussing such matters as reporter genes, gene activity, pigmentation, and the impact of environmental factors on the research.
Cone’s current research seeks to understand the function of a group of genes called chromatin: “Chromatin is the complex of DNA and protein, which allows us as humans–or plants like corn–to pack a lot of DNA into the tiny nucleus of a cell.” The DNA duplex for both corn plants and humans is huge. As she explains, “we have about the same size genome, about three billion base pairs, but ours is really long. We pack about six feet of DNA in every cell,” each of which is only five microns across. That’s a heck of a lot of DNA!” How does all that DNA fit in there? “We’re smart,” suggests Cone, adding that “corn and humans do it the same way,” as does every organism with a nucleus. Therefore, her research on DNA packaging is applicable to every organism, because “from yeast, to mice, to humans, to plants—we all wrap up our DNA basically the same way.” It amounts to a sort of microscopic compressor system, which Cone describes as “amazing.” If researchers can better understand how this chromatin packaging occurs, they might eventually be able to control the process to their advantage.
One of Cone’s earlier research projects on corn genetics is the Maize Mapping Project. Funded by the National Science Foundation as part of the Plant Genome Research Program, the project involved a collaboration of investigators at MU, the University of Arizona, and the University of Georgia. Of the four-year project that was completed in 2002, Cone recounts: “Our goal was to make a map of the maize genome.” Using molecular methods and a genetic population tailored specifically for the project, Cone’s research team set about placing DNA “landmarks” onto the chromosomes. “When we finally finished the map,” she says, “there were over 10,000 landmarks on it!”
According to Karen Cone, Professor of Biological Sciences, one can learn a lot about any kind of genetic organism by doing genetics in a model: “Maize is considered to be a model genetic organism because what we learn in this organism is translatable to others.” Because it is a plant, she explains, there is the added advantage of seeds that can go dormant, stored for years until one wants to run additional crosses with them. Maize has other positive attributes as well; for example, it has separate male and female parts, and every kernel is a baby. With just one cross producing 300 to 800 progeny on each ear, Cone finds maize to be an ideal organism for genetic research.
If researchers can better understand how this DNA packaging occurs, they might eventually be able to control the process to their advantage. As Cone observes, “being able to understand that process might give us a chance down the road to manipulate it, to potentially improve features of the plant for crop production.”
Cone teaches first-level genetics to biology and biochemistry students. “It is a lot of fun to teach introductory genetics,” she says, her enthusiasm obvious. She also teaches a capstone genetics course called “Human Inherited Diseases,” which explores the underlying molecular basis of certain inherited diseases in humans. “I’m not a human geneticist,” Cone specifies, “but I’ve learned about human genetics by teaching that class.” In addition to her teaching and research, Cone has done several major outreach projects.
“I don’t know exactly why I got interested in biology,” recounts Cone. “I was interested in medicine, so I started college thinking that I would be a medical doctor… But pretty soon I realized that wasn’t the kind of work that I wanted to do. So I started leaning more towards research.” Because of her own experience, Cone advises students accordingly: “You can turn out okay even if you don’t know what you want to do right now. So you just have to look for opportunities and keep your eyes open. Listen to what people are telling you, and to what sounds cool, and believe that nothing is impossible. In science it is common to totally change fields, to do your Ph.D. in one thing and eventually end up working on some other topic. Getting a Ph.D., after all, is about learning to be a critical independent thinker.”
This research on DNA packaging is applicable to every organism, Cone observes. Using the example of a calico cat, she explains: “Tortoise-shell and calico cats have orange and black fur patches on their body. That is due to a DNA packaging phenomenon.” As it turns out, the fur color gene is on the X chromosome. Just as human females have two X chromosomes, so do these calico cats, which are almost always female. In fact, they have one X with an orange-fur gene and one X with a black-fur gene: “so back when that little calico cat, with her different X chromosomes, was a 16 or a 32-cell embryo, in each cell, one of the X chromosomes got really tightly packaged, so tightly that the genes on that chromosome weren’t expressed.” If the X with the orange-fur gene is packaged, she continues, then the X with the black-fur gene remains active. As the cell divides further in the embryo, it will eventually give rise to a black patch of fur. The orange patches, of course, derive from the fact that in another cell, the X with the orange-fur gene, was the one left active, while the black one was balled up too tightly to be expressed. That is one concrete example of how DNA packaging influences whether or not a gene is turned on.
A graduate student in the School of Medicine’s Department of Molecular Microbiology and Immunology, Erica Racen works with professor Karen Bennett to study germline development in a small worm known as Caenorhabditis elegans. The germline are the cells that go on to become the next generation of the eggs or the sperm. “Our lab studies four proteins which are important for that development,” Racen explains. “When one of those proteins is missing, the worm becomes sterile.” Racen describes the worm in question, which is only one millimeter in length. Because it has a large germline, it is a good organism to study germline development.
“When I first started studying the protein GLH-1,” recounts Racen, “I knew it was important for fertility, but I did not know why. So I started to look at what things are different when GLH is missing. I found a relationship to the protein Dicer, that when GLH-1 was missing, so was Dicer. I also found that when Dicer was missing, so was RNA.” Trying to understand this relationship, Racen has conducted a series of experiments. She describes an actual experiment, one that involves mutants in which the gene has been knocked out or uses the process of “RNA interference” (injecting double-stranded RNAs into the worm, so that in the next generation those proteins are not produced). In this manner, Racen is able to study different genes in the worm.
Racen describes “a typical day in the lab,” providing a tour of Karen Bennett’s lab and showing some of the equipment used for her experiments. A typical day begins at sunrise when Racen plans her experiments, and will likely involve grinding worms to extract the cell lysate and problem solving with colleagues doing similar experiments.
Racen refers to her research as basic science. While the protein she works with is also found in humans, as of now there are few direct applications of this kind of research. Racen explains, however, “The more we learn about basic science, it will help us develop better treatments down the road. If we can understand how an egg develops from the very beginning, including all the proteins involved, we will have a better understanding of how to treat it.”
Keller’s work in the realm of bioinformatics-trying to make sense of microray experiments with DNA and cancer treatment.