Michelle Starz-Gaiano’s research on fruit flies seeks to uncover biological mechanisms driving embryonic development and is applicable to a variety of contexts. For example, her findings may help scientists and doctors better understand how cancers metastasize, leading to more effective treatments.
Starz-Gaiano, associate professor of biological sciences at UMBC, just received a three-year National Science Foundation grant to pursue research on a step in early fly development when a small cluster of cells migrates from one end of the developing egg to the other. While scientists have long understood that the process is driven by a chemical gradient—a higher concentration of a chemical signal at one end of the egg than the other—Starz-Gaiano thinks migration is more complicated than current models predict. “I don’t think the signaling molecules are where we expect,” she says.
The developing egg is bounded by follicle cells, with polar cells at each end of the egg. During early development, a cluster of these cells migrates, which is critical for normal development. This step is similar to metastasis, the process cancer cells undergo when they detach from a tumor and travel through the bloodstream.
In previous studies, Starz-Gaiano was surprised to find that the cells intended for migration did not form in the egg boundary symmetrically. That suggested that they were not uniformly receiving the protein that signaled migration.
Starz-Gaiano hypothesized that the cells beneath the polar cells were not in fact like dice laid end-to-end, with no spaces, as some scientists presumed. Instead, they were more like marbles, creating clefts between cells where the signal molecule could be trapped, therefore altering the selection of migrating cells and the start of the cell migration process.
Starz-Gaiano and collaborator Brad Peercy, associate professor of mathematics at UMBC, built a computer model to simulate the marble-like arrangement. Sure enough, the model recreated the asymmetrical cell pattern Starz-Gaiano and her students saw in real fruit flies, a result they published in 2015.
To validate the computer simulation, Starz-Gaiano’s new research calls for extensive imaging work with another collaborator, Tagide deCarvalho, director of UMBC’s Keith R. Porter Imaging Facility. Their goal is to identify individual signaling proteins within the egg to see if pools show up in the spaces between cells.
The standard cell migration model also ignores the fact that there are a lot of other cells in the way as the migrating cell cluster travels from one end of the egg to the other. This cellular obstacle course affects the migrating cluster’s path and speed, as well as the location of the signaling molecules throughout the egg. “The tissue landscape may be influencing signaling in ways we’re not appreciating,” says Starz-Gaiano.
The series of chemical reactions that controls cell migration in Starz-Gaiano’s fruit flies is markedly similar to what happens in other animals, including humans, so “it’s the perfect system for exploring this idea,” says Starz-Gaiano.
Starz-Gaiano points out that the passage of drugs through the body is likely also influenced by the structure of surrounding tissue. Understanding how surrounding cells affect the course drug molecules take through the body could lead to drugs that interact more actively with the blood vessels and organs they pass through, possibly increasing the amount of the drug that reaches the target, reducing required dosage and side effects.
Starz-Gaiano is excited to get started on the new project. Though challenging, it has the potential to create a paradigm shift in the cell signaling field. “It was a vote of confidence to be recommended for the grant,” Starz-Gaiano says, “and I can’t wait to get the answers.”