Research Laboratories
CELLULAR GENETICS (Takaomi Sakai, Satomi Takeo, Tsunaki Asano)
Research Overview
We study complex biological phenomena such as brain and nervous system functions at molecular, cellular, and individual levels using the Drosophila model system. Our primary research centers on the neurogenetic studies of instinctive and learned behaviors where we conduct research how these behaviors are regulated in the brain.
Drosophila melanogaster has well-developed genetics, with many available mutants and various gene expression tools already understood. Using fly genetics, we can not only analyze gene function, but also artificially excite or inhibit specific neurons. Furthermore, it is possible to visually identify which neurons in the brain are active. Using this state-of-the-art technology, we are conducting research on instinctive and learning behaviors.
Some of the work we do involve isolating a large number of mutants that exhibit various behavioral abnormalities as adults (sexual behavior, sleep rhythm, social behavior, feeding behavior, etc.) despite having no specific genetic developmental abnormalities. We then look at the different aspects of these behaviors using various experimental molecular biology, behavioral analyses, and brain imaging analysis. In addition, we are studying the the mechanisms underlying the acquisition and maintenance of long-term memory in Drosophila using courtship behavior.
If you are interested in joining the graduate program and doing research with us, please contact us through email.
Current Projects
(1) Elucidating mechanisms of long-term memory maintenance regulated by ambient light
Animals acquire memories through their experiences and maintain them for survival. Although the molecular mechanisms of memory acquisition have been studied in many animal models, the mechanisms of long-term maintenance of acquired memories remain poorly understood. We initially discovered that Drosophila flies utilize ambient light to maintain long-term memory, and we have pursued that area further to understand how. We later on found that light-induced release of the neuropeptide PDF (a type of neurotransmitter) activates a transcription factor called CREB in the memory center of the flies, which lead to the expression of a novel gene in the memory center that maintains long-term memory. This finding indicates that the maintenance or loss of long-term memory can be controlled by modifying the supply of ambient light or via genetic manipulation. At present, more research is underway to identify molecular targets of CREB.
Long-term memories, once acquired, may not be easily forgotten and could be difficult to erase. This can become problematic in that negative memories, such as those caused by trauma, can persist in animals and continuously impair their lives. Our research results may contribute to the development of traumatic memory erasure technology in the future.
(2) Molecular and neural mechanisms of long-term memory consolidation
Animals acquire plenty of memories throughout the day, but forget most of them the following day. On the other hand, new memories acquired through highly impactful or repetitive experiences are converted into stable long-term memories. This process is called "memory fixation". Memories that are not fixed are maintained in the brain for only a short period and are then erased. However, once consolidated, they are preserved in the brain as long-term memories for an extended duration.
In flies, a brain region called the "mushroom body" is thought to be the memory center. This mushroom body plays a role in flies similar to that of the hippocampus in mammals. The transcription factor CREB is thought to be essential for consolidating long-term memory in many animal species. It is believed that during the learning process, proteins synthesized by CREB activity are responsible for consolidating memories into long-term storage. We have identified several genes that are not expressed in the mushroom body but are essential for long-term memory consolidation. Interestingly, those genes were expressed by specific neurons in the brain called ''clock neurons". These neurons specifically express the "clock genes" that are necessary to produce the ~24-hour cycle in the behavior and physiology of the fly, and are thought to contribute primarily to the generation of circadian rhythms. We are currently working to elucidate the relationship between the clock neurons and memory centers as well as to understand the functions of the multiple genes we have identified.
Our findings will not only enable us to shed light on the novel functions of clock neurons, they will also contribute to the understanding of the molecular mechanisms behind long-term memory consolidation.
(3) Stress-induced suppression of sexual behavior: A Drosophila model for traumatic memory
Staff Highlight
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Dr. Takaomi Sakai (坂井 貴臣) Professor | Dr. Tsunaki Asano (朝野 維起) Assistant Professor | Dr. Satomi Takeo (武尾 里美) Assistant Professor |
Email: | ||
sakai-takaomi[at]tmu.ac.jp | asano-tsunaki[at]tmu.ac.jp | takeo-satomi[at]tmu.ac.jp |
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Lab Information: | ||
Recent Publications
1. Epoxide hydrolases JHEH1 and JHEH2 deficiency impairs glucose metabolism in Drosophila
Felipe Rogalsky, Manabu Tsuda, Satomi Takeo, Tsunaki Asano, Takaomi Sakai, Toshiro Aigaki. Biochemistry and Biophysical
Research Communications, 748 151313, Feb 2025
Teng Hu, Yasuro Furuichi, Yasuko Manabe, Kenichiro Yamada, Kengo Katakura, Yuna Aoki, Kun Tang, Takaomi Sakai,
Nobuharu L. Fujii. Molecular Biology Reports, 51(1) 1143, Nov 2024
3. Impact of Drosophila LIM homeodomain protein Apterous on the morphology of the adult mushroom body
Hikari Nakano, Takaomi Sakai. Biochemistry and Biophysical Research Communications, 682 77-84, Nov 2023
Hiroki Hamaguchi, Kitora Dohi, Takaomi Sakai, Masato Taoka, Toshiaki Isobe, Tsubasa S. Matsui, Shinji Deguchi,
Yasuro Furuichi, Nobuharu L. Fujii, Yasuko Manabe, Biochemistry and Biophysical Research Communications, 639 169-175,
Jan 2023
Show Inami, Takaomi Sakai. Neuroscience Research, 185 : 62-66, Dec 2022
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