Fruit fly study offers clues to wound healing

Published on April 6, 2013 at 2:27 AM · No Comments

A person's skin and a fruit fly's exoskeleton, called a "cuticle" may not look alike, but both coverings protect against injury, infection, and dehydration. The top layers of mammalian skin and insect cuticle are mesh-works of macromolecules, the mammal version consisting mostly of keratin proteins and the fly version predominantly of the carbohydrate chitin. Yet the requirement of an outer boundary for protection is so ancient that the outermost cells of both organisms respond to some of the same signals. And because of these signaling similarities, the fruit fly Drosophila melanogaster serves as a model for wound healing.

A presentation at the Genetics Society of America's 54th Annual Drosophila Research Conference in Washington D.C. April 3-7, 2013 describes a new way to study wound healing in flies that suggests new targets for wound-healing drugs. About 177 million people a year suffer from a wound, an opening that breaks the skin and usually damages the tissue underneath, which may be surgical, traumatic as a burn or laceration, or may be a chronic condition, as with people who have diabetes or those with immune system diseases.

Michelle T. Juarez, PhD, an assistant medical professor at the Sophie Davis School of Biomedical Education at the City College of New York, presents the doctoral research on wound healing of Rachel A. Patterson, from the University of California, San Diego (UCSD). William McGinnis, PhD, distinguished professor of the section of cell and developmental biology at UCSD, completes the research team. He has been investigating the "biological armor" of the fly for many years.

A desire to understand more about wound healing in people inspired the trio, particularly Ms. Patterson. "My fianc- is a firefighter and a member of the U.S. military. Maybe one day our work will influence his medical treatment if he sustains burns or injury wounds," she said.

The fly is an excellent model to dissect skin repair at a cell and molecular level. "Many of the key molecules and proteins involved in Drosophila wound healing are involved in mammalian wound healing. The genetics of Drosophila is not as complicated as mammalian genetics, so it's easier to attribute specific biological functions to individual genes," explained Ms. Patterson. During healing, molecular signals bind to receptors on the cells that line a wound, influencing the cell division, growth, and migration that restores the barrier.

To study the biological function of wound healing, the researchers needed to develop a "clean puncture wounding" protocol to damage the epidermis of fly embryos without allowing bacteria to infect the breach, which would complicate the study. Researchers study fly embryos rather than adult flies because it's easier and the embryos offer a wider range of genetic mutations than adult flies. The first step was to collect fly eggs, which contain developing embryos, and bleach them to remove the shells. Next they impaled the embryos with microneedles, like using a toothpick to spear an olive.

Key to the technique was injecting trypsin, a member of a family of enzymes called serine proteases, which control cell-to-cell signaling. Trypsin activates genes involved in wound healing throughout the embryo, and it also amplifies the response in the affected cells, revealing new players in the choreography of healing. "We took advantage of trypsin as a powerful wounding tool to pinpoint which genes are 'turned on' versus which genes are 'turned off' after wounding," Ms. Patterson said.

Researchers then looked at which genes were turned on and off at 30, 60, and 120 minutes post-stabbing that illuminate events as the borders of a small, clean wound close. The researchers were surprised to discover that an immune response begins as soon as the cuticle has been breached, with signals that prepare the embryo should bacteria or fungi enter soon after the injury.

Using microarray technology to assess gene action, the researchers surveyed 84 genes that are turned on and 78 genes that are turned off as the fly embryo responds to wounding.

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