A database about the tiny fruit fly

For more than a century, the humble fruit fly has paved the way for many critical scientific breakthroughs.

This tiny insect helped researchers figure out that X-rays can cause genetic mutations. That genes are passed on from parent to child through chromosomes. That a gene called period helps our bodies keep time — and that disruptions to that internal clock can lead to jet lag and increased risk for neurological and metabolic diseases.

Those discoveries, along with nearly 90,000 other studies, are part of a key online database called FlyBase that researchers routinely use to help them more quickly design new experiments. These tests explore the underlying causes of disease and could help with the development of new treatments. Science builds on prior insights, and a handy repository of past advances serves as kindling for future discoveries.

The website receives about 770,000 page views each month from scientists working around the world on developing personalized therapies for rare cancers, modeling human neurodegenerative diseases and screening drug candidates for conditions like Alzheimer’s.

Now, that critical resource is on the brink of layoffs that endanger its future and ability to make research more efficient.

This spring, the Trump administration, as part of its broader $2.2 billion funding cuts at Harvard University, rescinded a grant used to maintain FlyBase.

“I use FlyBase every single day. It’s so essential,” said Celeste Berg, a professor of genome sciences at the University of Washington, who is not part of the team that operates FlyBase. “What we know about human genes and how they function comes almost completely from model systems like drosophila.”

Humans share about 60% of our genes with fruit flies, also known by their scientific name Drosophila melanogaster.

FlyBase’s now-uncertain future highlights just how interconnected and interdependent research efforts are and how the effects of funding cuts to one institution can ripple worldwide. More than 4,000 labs use FlyBase.

Harvard was receiving about $2 million a year in federal funding to maintain FlyBase, which was the vast majority of the website’s total operating budget. But the University of New Mexico, Indiana University and the University of Cambridge in England are partners that help Harvard manage FlyBase and are beneficiaries, too.

“This is not just affecting Harvard,” said Brian Calvi, a professor of biology at Indiana University, who is part of the FlyBase management team. “The ripple effect is to the international biomedical research community.”

Harvard’s Faculty of Arts and Sciences rescued FlyBase with interim funding, but that support will cease in October, according to Norbert Perrimon, a professor of developmental biology at Harvard Medical School.

A judge earlier this month ordered the Trump administration to restore funding to Harvard researchers who lost grants, but money has not begun to flow to FlyBase, Perrimon said. The administration has promised to appeal the decision, which could halt the flow of funds.

The White House did not respond to a request for comment. The U.S. Department of Health and Human Services, which oversees the National Institutes of Health, declined to comment.

The Transmitter, a neuroscience news site, first reported about layoffs at FlyBase. The Harvard Crimson reported about the Harvard Faculty of Arts and Sciences’ decision not to continue with interim funding.

Calvi said the FlyBase grant provided full or partial salary for eight people at Harvard, three at Indiana, five at Cambridge and one at the University of New Mexico. Both Indiana and Cambridge were able to secure funds to keep their portion of the program operating into next year. The New Mexico position ended in August.

FlyBase, which has been operating since 1992, has received federal support for more than three decades. It curates and summarizes research papers, organizes findings about particular genes, and catalogs information about fruit flies that have been modified genetically to tease apart how certain genes guide normal development.

Fruit flies are among the most important animal models for biomedical research because scientists have been able to map their genomes and brains. They’re also relatively easy and cheap to handle.

Berg, the genome sciences professor and avid FlyBase user, studies human development and how cells form organs. FlyBase allows her to search and identify genes of interest for experiments. She then tests how changing the expression of those genes affects the arrangement of cells.

Every year, thousands of fruit fly papers are added to FlyBase and summarized. Without FlyBase, Berg said researchers and clinicians would struggle to keep up and could miss key connections about particular genes.

Researchers with the Undiagnosed Diseases Network use FlyBase to help identify whether genetic mutations in children could be contributing to rare and unexplained diseases. The scientists identify genetic variants in these patients and then compare those mutations to past research of those genes in flies.

FlyBase is now crowdfunding support on its website.

“Given the importance of FlyBase to the broader U.S. and international scientific research community, we are hopeful other institutions and other stakeholders at Harvard will support those efforts,” said James Chisholm, a spokesman for Harvard Faculty of Arts and Sciences, adding that several Harvard departments were “actively working to identify and secure additional funding to safeguard FlyBase’s operations.”

Two Harvard-based staffers have already been laid off from their work at FlyBase, and another six are scheduled for layoffs later in September and in early October, Perrimon said.

“If we cannot retain the key personnel, it’s going to be very difficult to get back those people who have knowledge to keep the databases running,” Perrimon said. “That would be the point of no return for FlyBase.”

The funding disruption is also threatening plans to move FlyBase’s data to a new long-term home called the Alliance of Genome Resources. Fruit flies are among several common “model organisms,” along with rats, mice and worms, that are used in laboratories and lay the groundwork for understanding human biology.

The National Institutes of Health has spent about $5 million a year since 2017 to merge several databases, including FlyBase, WormBase and the Mouse Genome Database, among a handful of others. Each contains information that human health researchers can cross-reference to study genes important for human health more efficiently.

“If you’re studying human genes and you have to study everything that’s known, you have to go to all of these [websites] and learn the system,” said Paul Sternberg, a professor of biology at the California Institute of Technology, who is leading the Alliance effort. “We want one-stop shopping.”

The Alliance’s budget expired June 30, and Sternberg said he is awaiting a funding renewal decision from NIH himself. He said the funding disruption at FlyBase represents a new, unexpected obstacle to making research findings more useful and easier to scour.

“We need to do this fast, but when you’re losing staff and energy, that’s what makes it dicey,” Sternberg said. “Don’t throw extra roadblocks. That’s all we ask.”

FlyBase had planned to merge with the Alliance in 2029. Now, Calvi and others are pushing for a speedier merger, before FlyBase’s financial runway runs out. The donations the organization is seeking are meant to help pay for that.

“So far it’s less than $100,000,” Calvi said of the organization’s crowdfunding efforts. “We probably need a million.”

Continue Reading