Futia says the initial reaction from his family was, “Why yeast? Don’t we already know everything about yeast?”

That confusion is what fueled Futia, a biology major and chemistry minor, to continue his research on mitochondrial variation in yeast at Binghamton University. It also led to a grant from the National Science Foundation’s Graduate Research Fellowship Program, which will provide funding for his work when he begins graduate school at Stanford University this fall.

So, why yeast? “If you want to learn how a Ferrari works,” Futia says, “you start by looking at the engine of a lawn mower. Yeast is our lawn mower.”

Working with yeast, a single-celled organism, provides biologists with more freedom and power in cell manipulation. Within the cell, Futia studies the mitochondria, which is responsible for energy production and metabolism regulation. The cells of all animals, including humans, have mitochondria. Yeast serves as a model organism, allowing scientists to extrapolate data and apply it to other populations.

Heather Fiumera, assistant professor of biological sciences at Binghamton University and Futia’s research advisor, heads a lab that focuses on mitochondrial genetics. Studying mitochondrial genomes might explain why two people differ in athletic ability, or help researchers understand more about mitochondrial diseases.

Mitochondria carry their own DNA, separate from the DNA in the nucleus. Molecular biologists believe this is a result from a large cell engulfing a smaller cell, incorporating two sets of DNA into a single cell, which then evolved so that all animals have separate mitochondrial DNA.

Unlike animals, yeasts reproduce by budding, a type of cloning. For years, scientists thought that through cloning, the daughter cell would have the exact same mitochondrial DNA as the parent cell. “We found that that wasn’t the case,” Futia says, “and no one has really definitively proved this before.”

Futia is incorporating these results into a research paper. He has also presented his research at Binghamton, as well as a yeast genetics conference in Seattle.

For Futia, the most challenging part of his independent research has been finding the right questions to ask. “When somebody finds a good question,” Futia says, “and nobody’s answered it yet, and they have idea about how to solve it, then they found gold.”

There’s a method to coming up with good questions, and there’s a reason Futia has been asking them. “He’s inquisitive and mentally prepared,” Fiumera says, “and a prepared mind gets lucky.”

Binghamton University biologist Heather Fiumera thinks that some of those health problems may lie in the fact that mitochondrial function requires the cooperation of two different genomes. Every human inherits two genomes: one in the cell’s nucleus, which is a mix of mom and dad’s DNA, and a different one in the mitochondria (the cell’s powerhouse), which contains a replica of mom’s mitochondrial DNA. “It may be that some combinations of mitochondrial and nuclear genomes work together more efficiently than others,” Fiumera says. “While mutations in either genome may affect mitochondrial function, they don’t explain the whole story. You might inherit a mitochondrial genome that helps you become a world-class marathon runner, but your brother” — who would have the exact same mitochondrial genome as you — “might not be as successful, even with the same training.” Similarly, a mitochondrial mutation may cause a severe metabolic disorder in one sibling, but mild symptoms in another, because of how the mitochondrial mutation interacts with their different nuclear DNAs.

Fiumera and her colleagues received a $1.25 million award from the National Institutes of Health (NIH) to explore the importance of these genetic interactions. The five-year grant will help Fiumera scale up the studies she is already doing in yeast. “We’re swapping mitochondrial genomes and seeing if it affects how our yeasts grow,” Fiumera says. “And we are finding that it really matters.”

Kristi Montooth, a biologist at the University of Indiana, says the work may help to illuminate why metabolic diseases are so variable and unpredictable. “There are mutations in mitochondrial genomes that, on their own, don’t have a negative effect,” she says. “But brought together with certain nuclear genomes, there’s a synergistic effect that causes them to function badly.”

The problem goes back to the evolutionary origins of the mitochondrion. Scientists believe that a mitochondrion has its own DNA because it was once a free-living bacterium that was engulfed by another cell. But instead of becoming dinner, the mitochondrion was co-opted to provide energy for its predator. The two cells managed to work together and, over time, became dependent upon one another. Mitochondria have inserted some of their genes into the nucleus, and the nucleus uses protein messengers to control how much energy the mitochondrion produces and how it does its job. It may be that the two genomes are still co-evolving and still learning the best ways to live together peacefully.

“Heather’s exploiting a lot of the genetic and genomic tools that yeast offers to take this to the next level,” says David Rand, who studies the coevolution of nuclear and mitochondrial genomes at Brown University. “The ability for Heather’s experiment to track down the interactions is going to be quite powerful.”

Yeast is a single-celled fungus with some powerful genetic tools that allow Fiumera to mix and match mitochondrial and nuclear genomes. Are there special combinations that allow better mitochondrial performance? Does “strain A” work better with mitochondrion 1 while “strain B” works better with mitochondrion 2? Fiumera will decide which combinations thrive best by subjecting her yeasts to a variety of unpleasant environments — including heat stress, oxidative stress and low-nutrient conditions — and measuring how well the mito-nuclear hybrid strains grow.

Montooth says previous studies have focused on swapping mitochondria between different species of yeast. But by looking at the variation within just one species and exploring how that variation relates to dysfunction, Fiumera’s work is more relevant for studying human disease.

So far, Fiumera’s preliminary studies have shown that the mitochondrial-nuclear interactions are responsible for as much as 20 percent of the differences in growth rates between strains. “That’s huge,” she says. Until now, Fiumera and her team have managed to look at the interactions among only a handful of strains. The NIH grant will help to buy laboratory equipment that will measure growth rates in about 200 samples at once, helping Fiumera to test hundreds of different yeast strains. She predicts they will collect more than 10,000 growth rates in just the initial phase of the project.

The second part of the experiment will be to map the genes involved in determining whether a combination is effective or ineffective. Fiumera says she’d eventually like to see whether beneficial combinations are more common in wild yeast populations; if mitochondrial-nuclear interactions are as important as biologists expect, it is likely that natural selection favors different combinations in different environments.

But Fiumera won’t be doing all of this work alone. “This project is a marriage between yeast genetics and population biology, and it is enhanced by my actual marriage to a population geneticist,” she jokes, referring to her husband, Binghamton biologist Anthony Fiumera, who will be collaborating on the project. Binghamton computer scientist Kenneth Chiu will lend his expertise to help the biologists parse through huge data sets.

Since energy production is so vital to a cell’s functioning, mitochondrial genes and machinery tend to be highly similar in organisms as far flung as yeast and humans. That allows Fiumera to hope that one day her research will be used to devise treatments for people who are suffering from debilitating metabolic disorders.

“You have to understand the mechanism behind a problem,” she says, “before you can fix the problem.”