When Assistant Professor of Biology Joseph Coolon walks outside on a warm summer day, not only does he marvel at the incredible beauty of the natural world, he is struck with wonder at how, with the same kind of instructions, living things have become so incredibly diverse in form and function.
“I’m generally interested in traits, or phenotypes, and how they differ between individuals and between organisms,” Coolon said. “To study this, I take advantage of my training in genetics, evolutionary biology, and bioinformatics. Most of the questions we ask in my lab are centered on evolutionary genetics and evolutionary genomics, because the trait that I tend to focus on is gene expression, and we can use genomic and bioinformatics techniques to measure gene expression traits for the whole genome all at once.”
Coolon studies primarily the fruit fly, or Drosophila, and yeast in the genus Saccharomyces.
“Those are the primary organisms we use, and we study all of the genes in the genome at once, using new genomic and bioinformatics approaches to measure genome-wide gene expression,” he said.
Another part of Coolon’s lab focuses on a pair of genes in a species called Drosophila sechellia, which live on the Seychelles Islands, off the coast of Africa.
“These genes have evolved such that they allow Drosophila sechellia to eat a toxic fruit,” Coolon said. “It only lives on those islands, and it eats the fruit of a single plant called Morinda citrifolia, or ‘Noni.’”
Noni fruit is interesting, Coolon says, because although it produces insecticides, Drosophila sechellia has evolved a way to evade the toxic effects of those products.
“Work in my group has identified a pair of genes that have evolved that allow it to eat this fruit,” Coolon said. “And this is a nice model for how insect crop pests might evolve resistance to pesticides used in agriculture, or how traits might evolve in nature more generally…. So about half of the lab is focused on answering very general basic science questions about how gene expression works, and how it evolves, and then the other half is looking at this case study, focusing on Drosophila sechellia and its evolved resistance to a naturally occurring pesticide.”
Since the very beginning of genome research, the humble fruit fly has been a grand cornerstone in learning how genes work together to make a viable organism. It should come as no surprise that the fruit fly continues to be a participant in further genome research. Why, however, are countless generations of fruit flies, and other organisms for that matter, being used at all?
“One motivation is that changes in gene expression are responsible for a large number of human disease traits,” Coolon said. “By understanding the genetics of changes in gene expression, we can learn about how things like cancer, Alzheimer’s and heart disease create those disease traits. So that’s one motivation—understanding disease at a basic level. Another motivation for me is I’m very fascinated by the diversity of life that you see when you walk outside. And so, a major contributor to that diversity in traits that you see, beautiful butterflies and colorful birds, all the amazing things you see when you step outside, a major contributor to that are changes in gene expression.”
Coolon’s third motivation is perhaps a less expected one, but one that is crucial to human survival.
“We need to feed the planet, and in order to do that we need to stop insect crop pests from eating our crops,” he said. “So, we’re focusing on an evolved pesticide resistance to start to answer questions about how insects might evolve resistance to pesticides.”
Clearly, genetic research is key in solving many issues that plague our species and the earth as a whole. Unfortunately, one can’t just pick up stinging nettles and mint leaves and determine which genes are responsible for making one of them cause you pain. This is where the data-heavy part of the research comes in.
“We need to be able to measure gene expression,” he said. “We can do that in a number of ways. Some amount of the work involves looking at allele-specific gene expression, where we take advantage of new, next-generation sequencing technology that allows us to generate hundreds of millions of sequence reads in a matter of days, and we can use that as a way to measure gene expression and allele-specific expression as well.”
Coolon looks forward to receiving a piece of equipment called a pyrosequencer, which will soon arrive on campus.
“It’s similar technology to that being used in next-generation sequencing, but we can use this to focus on individual genes in a low-throughput format that allows us to get very precise measurements,” he said. “We also use quantitative PCR—polymerase chain reaction—or real-time PCR to measure gene expression quite a bit for similar experiments.”
If you are interested in this kind of process, getting into the nitty-gritty of how genomic data can be used to figure out how living things tick, Coolon has some good news for you.
“I’m teaching a new course called Genomics Analysis next semester,” he said. “Genomics and big data are a huge shift in the way that we do genetics, with many people are moving into the area of genomics. And being able to do that and take advantage of these tools, I think, is a big deal for students.”