While some research into the origins of life focuses on pre-cellular life, Professor Holly Goodson in the Department of Chemistry and Biochemistry focuses her research on how cells change over time.
“Since cells are the fundamental units of life, if you really want to understand how evolution works, you need to know how cells evolve,” she said. “But I think conversely, if you want to know how cells work, you need to think about how the various parts of the cell came to be—how evolution works.”
Goodson, who has long been interested in how taking an evolutionary perspective to cellular biology and biochemistry can help scientists figure out how cells work now, has been at the forefront of establishing a field with the emerging name of evolutionary cell biology.
A typical molecular biologist or biochemist who wanted to understand how a protein works would potentially create mutations in the protein to find out which of them cause the protein to lose or alter its function. But when Goodson and other scientists in her field are studying a particular process, they will delete whole proteins to see which of those proteins are important for the process.
She uses nature’s mutagenesis experiments—the sequences of proteins in different organisms—to look at what cannot be changed for a cell to continue functioning.
“Kind of like if you have a car, and you don’t know how it works, you start pulling stuff out and say, OK, oh, if we take the spark plugs out, the engine doesn’t work, OK, that something really important,” she described. “Or, oh, if we detach this hose, the air conditioning doesn’t work, but the car still functions, so that’s something less important.
“While this is a useful approach, it is slow and costly. A more efficient approach is to compare lots of different related “vehicles” (organisms) to figure out what is common between them, develop hypotheses about what is important, and then perform experiments to test these hypotheses. ”
To demonstrate this concept within her field, Goodson discussed a protein called myosin. The protein is a molecular motor that makes muscles contract, but there are different myosins in different muscles: The myosin in an eyelid muscle is different from one in a gut muscle, for instance. As an evolutionary cell biologist, Goodson can decipher what makes the two different.
“What is conserved within the eye motors or gut motors, but different between them?” she said.
Molecular biologists don't have extensive training in evolutionary biology because they usually investigate questions from a chemistry or biochemistry perspective. It was yeast—though yeast and humans seemingly have little in common, they in fact do—that sparked Goodson’s curiosity about the interconnectedness between organisms. As a graduate student, Goodson found that yeast has similar myosin motors to ones in our guts, which was surprising because yeast don’t have muscles. They don’t even move.
She discovered that within the gut lining, these particular myosin motors are different from the muscle myosin motors, but they both bring food into the cell. Without considering what scientists learned about these motors in yeast, it would have been much harder to figure out what the human gut motors are doing, she said.
“Sort of a joke that’s not really a joke is that we’re just large colonies of yeast,” Goodson said, then laughed. “And then, to quote one of my students: ‘We are just large colonies of yeast with anxiety.”’
Many of her tools are bioinformatic, meaning she uses computers, mathematics, and biology to help analyze the data. Her work lays the foundation for designing drugs that target specific members of a protein family, which may reduce side effects for patients. The approach is also useful for the bioengineering field, because it will narrow down options that can then be tested experimentally.
While there is so much information now about biological sequences—details about the continuous molecules in a nucleic acid or protein—there was very little sequence information when she started as a graduate student, and the computer systems were slow. Now there’s a different challenge: There’s so much information that researchers have to spend more time limiting the parameters of their searches so that they don’t have to sift through too much.
“What’s really exploding now in a way that has never been there before is information about very strange organisms,” said Goodson, whose work is funded by the National Science Foundation and the Air Force Office of Scientific Research. “The diversity of life is becoming much more apparent. Understanding this diversity through evolutionary cell biology should help identify new ways to fight parasites such as malaria, supply inspiration for bioengineering, and provide insight into fundamental principles of living systems.”
Deanna Csomo Ferrell is Sr. Assistant Director of Marketing Communications in the College of Science, and editor of Catalyst.