Summer Plague or Scientific Miracle?

The fly swatting season has arrived. No sooner do you put your fresh strawberries on the counter than the first fruit fly arrives. It doesn’t take long for a platoon of Drosophila buddies to hover over the loot.

If you choose to swat, swipe, swat, backhand, or otherwise pursue your insecticidal tendencies, don’t waste a teaching moment. All you have to do is embrace that timeless maxim: know your enemy. As a staple of the laboratory, the fruit fly has proven to be an infinite source of biological inspiration and knowledge about how the brain and body develop and function.

Lesson One: Fruit flies have been around longer than we have — much longer!

Most likely, you will fail miserably in your zeal to repel your internal fruit flies. It’s not that you’re inept at drafting your deadly blows. It’s just that evolution has honed the cerebellum, wings, sensory systems, muscles and internal organs of the flies in the art of survival for about 40 million years. That’s 38 million years more than it took us Homo sapiens to evolve from our Australopithecus ancestors. Fruit flies have been in the school of evolution much longer than mankind.

Lesson two: Fruit flies have a cult following in science.

In the early 20th century, one of the first researchers to embrace this unwitting gift to science was Columbia University’s own giant in the history of genetics, Thomas Hunt Morgan. In 1910 Morgan noticed in Schermerhorn Hall on Amsterdam Ave. that he could easily recognize mutationslike big white eyes instead of the usual big red of the flies. He and his lab colleagues learned how to link these physical mutations to specific genetic stretches along the insects’ chromosomes.

Since then, these tiny arthropods have remained beloved and revealing research partners. For much of what we know about genetics, inheritance, biological development, sensory science, many diseases, and countless other facets of biology, we owe fruit flies. A recent study of the fruit fly research community said an estimate of more than 6,000 “aircraft workers worldwide appears to be conservative.”

Lesson Three: Fruit flies are Teeny Houdinis.

When threatened, a fruit fly can react almost immediately. To make basic evasive movements, the insect, even in its larval stages, must accurately track where its body is in space. This sense of body-place common to all animals is called proprioception. For example, it allows people to know where their limbs are without looking directly at them and to make fine adjustments during each movement, such as reaching for a strawberry.

Wesley Grueber, PhDand his colleagues at Columbia’s Zuckerman Institute found that a collection of sensory cells in the fly makes it possible to accurately track where different body regions are during movement.

dr. Grueber points out that similar cells and circuitry likely kick in when flies make aviation escape sequences that require you to swear in the kitchen. That is, unless your deftly executed backhands crush the fleeing fruit flies, turning their former and wonderful marriage of form and function into entropic functionless spots.

Lesson four: Fruit flies have 1,600 eyes, sort of.

If you could search the aftermath of a smashed fruit fly 580,000 or so cells, you would find at least some of the 800 light-harvesting facets, or ommatidia, that make up each of a fly’s eyes. You might also find remnants of the 200,000 neurons that make up the fly’s nervous system and thus the circuitry it had used to see the world.

You would also wander in the territory of Rudy Behnia, PhD, a principal investigator at the Zuckerman Institute. dr. Behnia has teased, among other things the cellular circuitry and calculations underlying the color vision of fruit flies. “Spectral information in the world is very rich and flies could use it for object recognition,” as well as for determining the time of day and navigating with clues about the sun’s location from the color of the sky, says Dr. Behnia.

As evidenced by your terrible batting average when it comes to fly-squishing, your insect enemies know your murderous hand is coming. This information comes from signal delay circuitry built into the fruit fly’s visual system. When the first sensory signals change between ommatidia, as happens when your hand strokes a fly’s field of view, the resulting signal patterns deeper in the fly’s brain contain information about the direction your hand is moving.

Now add in the fly’s phototaxis, playing on its talent for detecting and moving toward ultraviolet light, and you have the neurobiological basis for an escape plan. “Since most objects in nature reflect rather than absorb ultraviolet radiation, the main source of natural UV is the open air,” explains Dr. Behnia out. That means if you’re a fruit fly and you notice a disease coming your way, you need to follow that UV out to the open air.

Lesson Five: Fruit flies do amazing math, all in their heads.

To chart their course through the world and escape trajectories in times of danger, fruit flies use external reference points, such as the position of the sun, along with some serious mental math.

“The flies do trigonometry,” says Larry Abbott, PhDco-director of the Center for Theoretical Neurosciences at the Zuckerman Institute. “It’s unbelievable.”

A fly’s mental calculations begin by representing vectors, mathematical arrows with angles and lengths that themselves represent the direction and speed of movement. dr. Abbott and his colleagues discovered that the flies use wave-like patterns of brain activity to encode these vectors. The amplitudes and phases of those neural wave patterns correspond to the lengths and angles of the corresponding vectors in real space.

“Flies perform the kinds of vector calculations often assigned in introductory physics classes, but they do it in ways not normally taught in such courses,” says Dr. Abbott, adding that he’s looking forward to meeting a new colleague at the Zuckerman Institute later this summer, dr. Gwyneth Map. She will investigate the neural circuitry that flies use to decide exactly which escape response to perform, for example if a threatening human hand invades their personal space.

Lesson Six: The same genes that grow humans grow flies.

A fly contains half a million cells spread over more than 200 cell types and organized into body parts ranging from the antennae on the front of its head to the hairs on the back. This sophisticated body plan originates from a fertilized egg thanks to just eight genes in the Hox family: the master conductors of development.

Over many years of research, Richard Mann, PhDanother Zuckerman neuroscientist who studies fruit flies teases how Hox genes, transcription factors and many other genes and proteins coordinate their flying skills according to a brilliant logic of biological development. What scientists learn about this logic in model organisms such as fruit flies often points to analogous developmental logic in humans, Dr. Mann says. He emphasizes that the genetic interfaces for humans and fruit flies goes beyond developmental genes. Mann says, “So many human genes are also found in flies, and most human disease genes are also found in flies.”

Lesson Seven: Fruit flies are symphonies of genetic and cellular notes.

Getting even more biological insight from fruit fly genes is the lead researcher at the Zuckerman Institute Minoree Kohwi, PhD. She identified the specific places and times at which developmental genes become active in successive generations of cells of a growing fruit fly.

“Think of each gene as a single musical note: By itself, a note is an isolated sound, but play each note at the right time for just the right duration, and you get a beautiful symphony,” said Dr. Kohwi.

One of the big questions she wants to answer is this: “How are the thousands of different cell types produced in such an organized way to allow proper brain function.”

Dr. Kohwi’s lab uncovers the origins of a fly’s many different cell types, helping to reveal the origins of a similar diversity of cells in its own brain. Her research digs deep into the molecular foundations of life by revealing how and when developmental genes migrate to different locations in the cell nucleus. These migrations control when specific developmental genes are active and when they are repressed. And those on-off sequences, Dr. Kohwi, “ultimately determining when each brain cell type can be made during development.”

Crush a miracle

Couple of Drosophila researchers would think twice about defending the fresh fruit on their tables with deadly force. But because of what they know about the wonders of fruit flies, you might see a flash of admiration for flies on their faces as soon as you hear thwap.

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