A Taiwanese research team reported its high-resolution 3-D interactive map of olfactory circuits in the fruit fly's brain and published its findings in the March 23 issue of the academic journal Cell, which focuses on molecular biology, biochemistry, genetics and neurobiology.
"It is the first time Taiwanese research has been published in that particular science journal," said research leader Chiang Ann-shyn May 23. "We were the first to map out clearly how the sensory stimuli are relayed in the third level of fruit flies' higher brain centers."
American Richard Axel won the 2004 Nobel Prize for Physiology or Medicine for his 1991 work on the completion of the neural coding for olfactory sensory stimuli in the fruit fly brain's first-level neural center. The Taiwanese research on second- and third-level brain centers represents further significant finds in the field of neurogenomics and a big jump toward understanding the mysteries of all brains, Chiang claimed.
Chiang, who received his doctoral degree from Rutgers University in the United States, is now director of the Institute of Biotechnology and director of the Brain Research Center at National Tsing Hua University in Hsinchu City.
"While many scientists were rushing to follow Axel in analyzing the first-level brain center, we keep wondering how we could go further in the same field. We therefore decided to explore the higher neural centers in order to get a more integral picture of how the brain perceives its environment," asserted Chiang. "Only by fully understanding different levels of processing centers can we possibly realize the intricacy of the brain," he added.
Titled "A Map of Olfactory Representation in the Drosophila Mushroom Body," the research paper used fruit flies to "represent the patterns of sensory stimuli by spatially distinct maps of activity at different stages of sensory processing," quoted the report. Chiang's team discovered that the antennae of fruit flies--their olfactory receptors--receive signals of smells from their environment and translate them into neural coding. These signals are transformed in the calyx of the brain's mushroom body, indispensable to learning and memory processing. The mushroom body then integrates and calculates signals that are subsequently relayed to higher processing centers inside the brain via a variety of pathways.
In other words, after signals are received, the multiple-layer processing centers filter the minor signals and intensify the major ones. The brain then computes the signals that enable fruit fly brains to make decisions or take action.
Another significant factor in this research is the patented bioimaging techniques developed by Chiang's team. "The first obstacle to overcome is how to observe gene-expression patterns in thick biological tissues," explained Chiang. His innovation for making tissues transparent without destroying their integrity derived from the fact that some transparent creatures, such as jellyfish and body lice, exist in nature. After years of trials, Chiang invented FocusClear, a water-soluble clearing agent that made biological tissues transparent, which has been granted a 20-year patent in the United States and several other countries.
Special equipment to visualize the transparent tissues was also required, so Chiang said he raised around US$300,000 to purchase Taiwan's first confocal microscope. This uses a laser to scan the tissue and reconstruct 3-D images in the computer, in comparison with traditional electron microscopes, which view 2-D images.
"Using these bioimaging technologies we are able to see tiny genes, which paves the way for further study of how genetic sequences are responsible for some brain disorders," he said.
"We manipulate fruit fly genes in our laboratory to make them suffer from various disorders such as Alzheimer's disease, depression and insomnia," said Wu Chia-lin May 23, an NTHU doctoral student who was advised by Chiang and involved in this groundbreaking research. By observing flies with particular genetic flaws using bioimaging technologies, the team could possibly unveil relations between patterns of genes and genetic diseases, noted Wu.
One reason fruit flies were used was the similarities between their genes and human genes, Chiang explained. Although a fruit fly carries only around 135,000 genes, which might seem few in comparison to a human being's 4 billion genes, a large number of genes that suffer from human genetic disorders can be found in the fruit fly. "Flies are cheap to breed, and their genes can be manipulated quickly," he declared. Moreover, better understanding of genes would allow scientists to search faster for novel therapeutic drugs for healing diseases like Alzheimer's, he added.
"Now we know how the first three centers in the brain work, but we still don't know how many levels there are. It's just like we don't know yet how many planets there are in the universe or how many systems behind our solar system there are," claimed Chiang. The ultimate goal of this kind of research is to construct an integral and independent graphic digital database of fruit flies' memory circuits at the cellular and molecular levels. This ambitious plan has attracted the interest of foreign academic institutions, including the universities of Harvard, Stanford and Vienna, which wished to cooperate with his team, Chiang said.
Despite its limited budget and resources, Chiang's research is evidently ahead of these institutes. The NTHU provided US$400,000 to fund Chiang's project, which is a tiny figure when compared to donations of US$500 million by the Howard Hughes Medical Institute and US$100 million by the Allen Institute for Brain Science to conduct research into the same field, Chiang claimed, adding that fulfillment of the project would require comprehensive collaboration from the academic, private and public sectors.
In fact, the latest breakthrough by Chiang and his team was achieved with cooperation from the U.S.-based Cold Spring Harbor Laboratory, a private research and education institution dedicated to the fields of cancer, neuroscience, genomics and bioinformatics, the BRC Web site stated.
The BRC also collaborated with domestic academic institutions, including the National Science Council, National Center for High-Performance Computing and National Chiao Tung University. The NSC is the highest government agency responsible for promoting development of science and technology, while the NCHC is devoted to high-performance computing hardware, software and networking resources.
Chiang admitted that his research was just a small step along the road to a comprehensive understanding of how the brain functions. "There's still a long way to go before the ultimate mystery of the human brain is solved," he said, "but whoever gets it will control the future of human beings."
rite to Allen Hsu at allenhsu@mail.gio.gov.tw