Better Biology Through Math

Biologists study questions ranging from how cells produce protein to why human beings act the way they do. One Penn professor is taking on the whole span: Associate Professor of Biology Joshua Plotkin and his research group recently published journal articles on both of those diverse topics.

Plotkin, who also has an appointment at the School of Engineering and Applied Science, uses mathematics and computation to study questions in evolutionary biology and ecology. His team was interested in what sets the pace of protein production: the “initiation rate” of how quickly the ribosomes start moving along the gene, or the “elongation rate” of how quickly they move. The researchers developed a “very, very detailed” computational model to keep track of the 30,000 or 40,000 entities involved, and discovered that in the vast majority of genes, it is the initiation rate that determines the pace.

“Proteins are the building blocks for all of life, so we wanted to know what the throttle point is,” says Plotkin. “Reconciling this was important to us because as evolutionary biologists it only made sense that the cell would be controlling protein production at the initiation rate. The ribosomes that produce protein are very costly for the cell to produce, so that having an oversupply of them would be wasteful.”

On the other hand, he and his associates used just “pencil, paper, and math” to expand understanding of the classic game theory model the Prisoner’s Dilemma. In the game, if both players cooperate, both receive a payoff; if neither cooperates, both receive a smaller payoff. If only one cooperates, the cooperating player receives a smaller payoff than the other player. In other words, it pays to cooperate, but it can pay even more to be selfish.

However, by assuming a population of players that changes and evolves, much as it would in life, Plotkin’s group showed that only generous strategies would succeed in the long run. The finding leads to other questions, such as what happens to a cooperative population when the environment changes: Does the fact that the population is cooperative make it more likely to adapt, or make it fragile and prone to extinction?

The two projects seem very different, and yet, “Somehow we all have lunch and happy conversations,” says Plotkin of his group. “It’s because in the end we are all interested in evolution: What happens in an evolving population? How does the way a cell evolved tell us what are the most important set points in protein production?”

Plotkin comes from a math background, but had second thoughts about his specialty partway through graduate school. “Being a professional mathematician is sort of like solving complicated crossword puzzles all day long,” he says. He’d taken a course in evolution in college, and decided he liked the questions it raised: “Everywhere you looked you could find a problem that begged explanation.” Members of his research group have backgrounds ranging from physics and biology to statistics and computer science. He’s also inspired by his fellow faculty, with whom he has “hallway conversations, sometimes chalkboard conversations, and once in a while an experiment.”

 “It’s just lots of fun,” Plotkin says of his work. “Most of our research requires a confluence of skills. When the group is diverse, it is so much more than the sum of its parts.”