Change and Survival
Graduate student Lucia Peixoto investigates the molecular machinery of single cell parasites.
Peter Nichols“I’ve always been fascinated by biology,” says Lucia Peixoto. “I knew I wanted to do research by the time I was 12.” She read Darwin’s Voyage of the Beagle before she was a teenager. Her father bought it on a business trip to Ecuador and carried it home to her in Uruguay. “Darwin had stopped in Uruguay quite a bit,” she notes, “so there are a lot of his sites there.” Peixoto, now a graduate student in biology, has visited most of them.
Today, the young evolutionary genomicist investigates the molecular evolution and function of single-cell parasites in the laboratory of David Roos, the E. Otis Kendall Professor of Biology.
“I think evolution most fascinates me,” Peixoto muses, lifting her hand. “Just imagine how wonderful it is that this hand right here—a really, really long time ago—was actually a fin.”
Peixoto’s wonder has led her to look deeply into how the molecular machinery of single cells works. To do that, she had to develop expert knowledge of computer programming as well as the skills needed to carry out laboratory experiments at the cellular and molecular level.
“How we do science in the genomic era is different,” she says. “You cannot just keep looking at one gene and ignore the rest of the genome, because when you look at the whole picture, you may get a different answer to your question.”
To understand the whole picture, scientists use computers to sort through and compare data compiled over the last decade by the sequencing of genomes from many organisms. Peixoto probes evolutionary history, which can be read by lining up, side by side, the genetic alphabet from many species and noting which genes have survived, which have not, and which have changed into new and improved versions. Using computational models of how genetic sequences evolve, investigators construct a tree of descent that predicts how a sequence came to be as it is now.
Computer analyses can recommend to researchers which genes and expression pathways might yield important knowledge if examined more closely. “Basically, evolution shows function,” she explains. “By looking at genomes through evolution, I look at how they have changed over time to make an inference about how important particular genes are for the organism and what their function might be.” The hypotheses that result from her number crunching then need to be tested and refined at the laboratory bench.
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One of the organisms studied in the Roos lab is the single-cell parasite Toxoplasma gondii, a major source of congenital neurological birth defects and an opportunistic infection that attacks AIDS patients.
Peixoto’s evolutionary analysis drew her attention to sets of duplicated genes in Toxoplasma, among them an extended family of protein kinases—enzymes that transfer phosphates between proteins. Phosphates can carry signals within a cell, Peixoto explains. When something happens on the cell surface that requires a response from the cell, a chemical message is transmitted to the nucleus. Kinases govern the signaling pathway inside a cell. A stimulus from the environment outside activates a protein kinase on the cell membrane, which then transfers a phosphate to another protein, which in turn passes a phosphate to the next in handoff that cascades all the way down to the nucleus.
Toxoplasma lives inside an individual cell, thus its host is essentially an environment for it. Peixoto was surprised to find that the kinases she was looking at were secreted out of the parasite and into the host cell. “That doesn’t make any sense,” she says, “except that by pumping out these kinases, Toxo now can change the signaling cascades of the cells they are living in, making the host cell an environment that is good for them.” In experiments using different strains of Toxoplasma, she found one kinase that, when added, made the host cell “freak out” to a lesser degree than it ordinarily would when invaded by the virulent parasite strain.
"Lucia's passion for evolutionary biology provides her with the motivation necessary for success in the newly emerging discipline of comparative genomics," Roos comments. "Her ability to explore the vast new datasets produced by genome projects, combining computational analysis with experimental studies at the laboratory bench, is enhancing our understanding of how parasites evolve and how they interact with their hosts."
“We are just a collection of carbon, oxygen, hydrogen,” Peixoto says, “organic molecules with a basic cell structure. This amazing complexity actually comes about through very simple processes of change and survival. It’s just so elegant. It’s just fascinating to look at.”