Buzzing with excitement, the “fly people” swarmed into Chicago this week to hear the latest news about an unsung hero of science: the humble fruit fly.
The public may see the insect mainly as a kitchen pest, but to the 1,500 scientists attending the 50th annual Drosophila Research Conference, Drosophila melanogaster is one of the most important research animals in genetics, an encyclopedia of knowledge packed into a critter a tenth of an inch long.
By breeding fruit flies, early 20th Century scientists figured out the location of genes controlling certain traits, creating the first crude genetic map. In 2000, Drosophila was the first multicellular organism to have its genome fully sequenced, providing a full blueprint of the organism.
With almost a century of fruit-fly research merging with new genetic technologies, the insect is poised to broaden human knowledge of diseases, including cancer and depression, and provide a cost-effective and efficient system for testing promising therapies.
Flies and humans share many genes and proteins, making the fruit fly ideal for unraveling biological mysteries.
“It’s very, very hard for the average person or congressman to really believe that when we look at an insect it has anything to do with them,” said Allan Spradling, an embryologist and Drosophila researcher at the Carnegie Institution of Washington. “But … an organism that seems so foreign and different from us really taught us a lot about our own selves and our genome.”
Politicians have been known to take potshots at fruit-fly research, most recently when Republican vice presidential candidate Sarah Palin cited it as an example of unnecessary earmarks at an October appearance. Though she was referring to a specific agricultural study taking place in Paris, Drosophila researchers were quick to defend their field, saying many fly projects were aimed at one of Palin’s favorite concerns — autism.
In truth, similar arguments on behalf of Drosophila could be made for virtually any human disease or behavior. Since 1910, when T.H. Morgan discovered a white-eyed mutant fly among his stock of wild-type red-eyed flies, scientists have been manipulating the flies’ genes to learn how they work — or fail.
In the Chicago area, at least a dozen fruit-fly laboratories operate on university campuses, studying such issues as sleep disorders, sexual orientation, evolution and gene therapy using the tiny insects.
Drosophila is so popular in part because researchers can breed and raise thousands of them very quickly and at a fraction of the cost of using rats or mice. A new generation of fruit flies can be created every 10 days, and females lay as many as 400 eggs during their lifetime.
In addition, exposing flies to radiation quickly creates random genetic mutations to study, and genetic tools can be used to flick genes on and off in fruit flies much more easily than in larger organisms.
“In spite of the hundreds of millions of years of evolution that have occurred between humans and Drosophila lineages, still 70 percent of the genes encoded in their genomes are similar,” said University of Chicago geneticist Kevin White. “So we’re able to use Drosophila … to very rapidly do experiments and genetic manipulations that you just can’t do in humans.”
Last week, White and other researchers from the U. of C. and Argonne National Laboratory, near Lemont, published a paper in the journal Nature on a project that combined fruit-fly genetics with the latest in data-mining systems to find a new genetic marker of kidney cancer in humans.
Drawing upon nearly a century of work mapping Drosophila genes and the way their proteins interact, the team narrowed thousands of candidate genes down to a single protein, called SPOP, that is associated with faulty development of fly embryos. When the researchers tested human cancer cells for SPOP, they found it in 85 percent of renal cell carcinomas, a common form of kidney cancer.
The discovery could lead to tests that would identify kidney cancer at an early stage, improving treatment outcomes for patients, White said.
The lives of fruit flies may also hold insight into human behavior. Ravi Allada, a neurobiologist at Northwestern University, uses the insects to study circadian rhythms, the mechanisms that control sleep cycles in flies and humans.
“The big picture is that if we understand more about which genes are important for our circadian rhythms or our sleep and understand how those genes work, it will give us a better understanding of diseases that may be the consequence of such systems going awry,” Allada said.
David Featherstone, a biologist at the University of Illinois at Chicago, stumbled on a peculiar fly model of human behavior when studying glutamate, an excitatory neurotransmitter in fly and human brains. Disrupting a gene in one part of the brain created male flies, nicknamed genderblind, that attempted to mate with both females and other males.
The finding may be relevant not only to research on sexual orientation but also to studies of muscle diseases and mental illnesses such as schizophrenia and depression where signals among nerve cells are disrupted, Featherstone said.
“We’re not just trying to figure out stuff to entertain people or fill textbooks with irrelevant minutia about how the brain works,” he said. “Ultimately we hope to understand the brain and gain the ability to engineer it.”
Richard Carthew, a developmental biologist at Northwestern, is using Drosophila to study how RNA interference might be used to silence genes and nullify infectious viruses. Even after a century, the potential for fruit fly research to benefit human health is still growing, he said.
“It’s a very traditional, long-standing lab animal, but it shows no signs of tiring. It has good legs,” Carthew said. “There’s really nothing comparable to it.”
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Naming mutants and genes: Now that’s entertainment
In any genetic field, researchers who discover a new mutant or gene earn the right to give it a name. But in the field of fruit-fly research, it’s a time-honored tradition to make that name as memorable as possible, leading to fly names that range from the whimsical to the bizarre.
When scientists at Argonne National Laboratory and the University of Chicago recently discovered a gene associated with renal cancer, they were using a strain of mutant fly named roadkill for its disorganized brain. Here are more examples from the entertaining Drosophila mutant gene pool:
Van Gogh: Rather than orderly wing hairs that all point the same direction, the hair bristles on Van Gogh mutants form swirling patterns, reminiscent of Vincent Van Gogh’s painting “The Starry Night.”
Kojak: Pity these poor flies — they grow no wing hair at all. That’s why they are named for Telly Savalas’ proudly bald television cop, Kojak. Who loves ya, baby?
Groucho: Continuing the hair theme, groucho flies grow an excess of hair on their faces, suggesting the mustachioed Marx brother.
Cheapdate: Flies, like humans, show telltale signs of drunkenness: first hyperactive and disoriented, then uncoordinated and sedated. Cheapdate mutants show inebriation at lower doses of ethanol, suggesting a lower tolerance for the drug.
Ken and Barbie: The sexual organs of these flies remain inside the body, producing doll-like private parts.
Kenny: Not to be confused with ken, this star-crossed fly dies quickly and violently — just as the red-sweat-shirted character on “South Park” — after being exposed to a particular type of bacteria.
INDY: An acronym for I’m Not Dead Yet, which refers to a classic scene from the film “Monty Python and The Holy Grail.” The life span of these flies is double that of a typical fly.
SOURCE: www.flynome.com
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Groundbreaking events in research on fruit flies
1910: T.H. Morgan (right) discovers the first Drosophila mutant, a white-eyed fly. His genetic experiments with such mutants won him the Nobel Prize in 1933.
1916: A mutant fly “monster” with two sets of wings is discovered. It became a critical piece of developmental biology research 60 years later.
1927: Using Drosophila, Hermann Muller discovers that radiation can cause gene mutations.
1958: The first Drosophila Research Conference is held in Madison, Wis. Total attendance: five professors and a handful of graduate students.
1971: Seymour Benzer and Ron Kanopka discover the genes that mediate circadian rhythms in fruit flies, proving the insect could be used to model human behavior.
1978: Studying double-winged mutants, Edward Lewis discovers a set of genes that control body development. The set later was found to control the development of mammals, including humans.
1987: The world’s largest collection of fly “stocks” is moved to Bloomington, Ind. The site now holds more than 25,000 stocks of Drosophila mutants and natural species available to researchers by mail order.
2000: The Drosophila genome is sequenced. It is the first multicellular organism to be fully mapped.
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rmitchum@tribune.com
