NSF Awards $12.5M to Duke Researchers and Colleagues to Explore Polyploidy

A new $12.5 million National Science Foundation grant was awarded to Duke University School of Medicine researchers and colleagues to investigate biology common to cancer, agriculture, biodiversity and more.  

It's called polyploidy, and only within the last few years have biologists begun to recognize its significance across the tree of life.  

“Polyploidy packs cells and organisms with extra sets of genetic material. It’s found in organisms all over the planet and in the cells of essentially every human organ system,” said Don Fox, PhD, professor of pharmacology & cancer biology and cell biology who leads Duke’s effort in the multi-institution project. 

Fox is one of 18 scientists working to establish the Polyploidy Integration and Innovation Institute. The grant is part of a broader initiative by the NSF to bring together scientists from disparate areas of expertise to work on pressing problems in biology.  

Don Fox, PhD
 Don Fox, PhD

The University of Florida and the Florida Museum will lead the project, collaborating with institutions including Duke, Cornell University, University of Kentucky, University of Minnesota, University of Mississippi, University of Pittsburgh, and the Ghent University and the Max Planck Institute for Plant Breeding Research. 

Fox’s laboratory will study polyploidy in an animal model -- the fruit fly.   

“We don’t know much about how polyploidy impacts biological processes. To answer this fundamental question, we needed a team approach,” Fox said.  

This NSF award enables Fox to combine his efforts in flies with colleagues in the U.S. and Europe, who will add studies in plants, algae, and fungi to the collaborative effort. “Polyploidy is a perfect topic for this sort of integration,” said plant biologist Pam Soltis, PhD, a curator at the Florida Museum and lead investigator on the project. Researchers with the institute will study the effects of polyploidy in plants and animals, from entire ecosystems down to organs and cells.  

“We want to conduct a set of experiments that is consistent across organisms,” said Doug Soltis, PhD, professor at the Florida Museum of Natural History and the Department of Biology at the University of Florida. “This is the first time we’ll be able to determine whether there are consistent rules that govern polyploidy.” 

The institute will use new and unique data management tools and prioritize community engagement to gain as much insight as possible, with eventual applications to agriculture, medicine, and conservation.  

“The institute will guide high school curriculum development and teacher training, provide research experiences for undergraduates, graduate students and post-doctoral researchers and offer training in science communication, while hosting local and international research conferences,” said Pam Soltis. 

Tip of the Iceberg  

At its most basic, polyploidy just means having more than the normal pair of matching chromosomes. Typically, when plants and animals undergo sexual reproduction, two sets of chromosomes — one from each parent — combine to create a new organism.  

Humans have been aware of this concept since the Austrian monk Gregor Mendel established the foundation of genetic inheritance by conducting experiments with pea plants. But occasionally, this process goes awry, and instead of a pair of chromosomes, offspring are endowed with additional chromosome sets in a process called genome duplication.  

This happens frequently in plants, and for several decades, botanists were the only ones who took a significant interest in the subject. The process can be so prevalent that some plants carry around eight or more chromosome pairs packed tightly in their cells. What is the utility of all this extra genetic material? Scientists once thought it didn’thave much use at all. Then they discovered it was one of the most common ways new species are formed. 

According to Soltis, they’re still learning this. “My own view is there are hundreds of thousands of cryptic polyploid species that we have never recognized or scientifically named.” 

For reasons that remain unclear, polyploidy also seems to be stratified on a global scale. There are fewer known polyploid species in the tropics than there are in colder regions, and the incidence of genome duplication appears to be higher at increased elevations.  

It may also have serious implications for how well plants are able to cope with rapid climate change.  

Biologists later discovered that polyploidy wasn’t just restricted to plants. Animals had it too. Nearly everything with a backbone can trace its origin to double genome duplication events that took place more than 450 million years ago. Similar duplications have occurred in fish, worms, insects, arachnids and mollusks.  

“Polyploidy is everywhere,” Soltis said. “It’s a giant iceberg, and we’re at the very tip.” 

Biomedical Implications 

Scientists next discovered that polyploidy did much more than increase biodiversity. It’s also an important part of the way many plants and animals function — or malfunction. Polyploidy is present in roughly 37% of cancer types in humans. In other types, scientists think induced polyploidy may even provide a cure. 

Polyploidy pops up in various organs as well, where it plays a significant role. “We’ve contributed to the finding that polyploidy promotes significant organ regeneration” said Fox, who co-directs Duke’s Regeneration Center. “And recently we collaborated with Dawn Bowles, PhD, in the Duke Department of Surgery and Nenad Bursac, PhD, in the Department of Biomedical Engineering to show that polyploidy shapes the chambers of the heart in both flies and humans. This means that polyploidy may play a critical role in sculpting not only the heart but many other organs.”  

The medical community began realizing the importance of polyploidy in the early 2000s, but they were largely unaware that other biologists had been intently focused on the topic for many decades. A series of scientific conferences devoted entirely to polyploidy helped bring everyone together.  

“It’s a case of not seeing what you don’t look for. We were all siloed, and there was a lot of surprise when people learned about what others were doing,” Soltis said.  

Just as genetics became its own field of study that transcended biological boundaries after Mendel laid out the laws of inheritance, polyploidy is poised to become a new specialty, one ripe for discovery and innovation. The Polyploidy Integration and Innovation Institute will help make this happen. 

In addition to Duke, the University of Florida, and the Florida Museum, other collaborating institutions are Cornell University, the University of Kentucky, the University of Minnesota, the University of Mississippi, the University of Pittsburgh, Ghent University and the Max Planck Institute for Plant Breeding Research. 

Content adapted from University of Florida.