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Search DetailsTAKEISHI AsukaGraduate School of Science / Division of BiologyAssociate Professor
Researcher basic information
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Research activity information
■ Paper- Springer Science and Business Media LLC, Dec. 2025, Scientific Reports, 16(1) (1), English[Refereed]Scientific journal
- Apr. 2025, Journal of Biosciences, 50(32) (32), English[Refereed][Invited]Scientific journal
- The mechanisms by which the innate immune system senses damage have been extensively explored in multicellular organisms. In Drosophila, various types of tissue damage, including epidermal injury, tumor formation, cell competition, and apoptosis deficiency, induce sterile activation of the Toll pathway, a process that requires the use of extracellular serine protease (SP) cascades. Upon infection, the SP Spätzle (Spz)-processing enzyme (SPE) cleaves and activates the Toll ligand Spz downstream of two paralogous SPs, Hayan and Persephone (Psh). However, upon tissue damage, it is not fully understood which SPs establish Spz activation cascades nor what damage-associated molecules can activate SPs. In this study, using newly generated uncleavable spz mutant flies, we revealed that Spz cleavage is required for the sterile activation of the Toll pathway, which is induced by apoptosis-deficient damage of wing epidermal cells in adult Drosophila. Proteomic analysis of hemolymph, followed by experiments with Drosophila Schneider 2 (S2) cells, revealed that among hemolymph SPs, both SPE and Melanization Protease 1 (MP1) have high capacities to cleave Spz. Additionally, in S2 cells, MP1 acts downstream of Hayan and Psh in a similar manner to SPE. Using genetic analysis, we found that the upstream SPs Hayan and Psh contributes to the sterile activation of the Toll pathway. While SPE/MP1 double mutants show more impairment of Toll activation upon infection than SPE single mutants, Toll activation is not eliminated in these apoptosis-deficient flies. This suggests that Hayan and Psh sense necrotic damage, inducing Spz cleavage by SPs other than SPE and MP1. Furthermore, hydrogen peroxide, a representative damage-associated molecule, activates the Psh-Spz cascade in S2 cells overexpressing Psh. Considering that reactive oxygen species (ROS) were detected in apoptosis-deficient wings, our findings highlight the importance of ROS as signaling molecules that induce the activation of SPs such as Psh in response to damage.Public Library of Science (PLoS), Jun. 2023, PLOS Genetics, 19(6) (6), e1010761 - e1010761, English[Refereed]Scientific journal
- Mechanical nonreciprocity, or the asymmetric transmission of mechanical quantities between two points in space, is crucial for developing systems that can guide, damp, and control mechanical energy. We report a uniform composite hydrogel that displays substantial mechanical nonreciprocity, owing to direction-dependent buckling of embedded nanofillers. This material exhibits an elastic modulus more than 60 times higher when sheared in one direction compared with the opposite direction. Consequently, it can transform symmetric vibrations into asymmetric ones that are applicable for mass transport and energy harvest. Furthermore, it exhibits an asymmetric deformation when subjected to local interactions, which can induce directional motion of various objects, including macroscopic objects and even small living creatures. This material could promote the development of nonreciprocal systems for practical applications such as energy conversion and biological manipulation.American Association for the Advancement of Science (AAAS), Apr. 2023, Science, 380(6641) (6641), 192 - 198, English[Refereed]Scientific journal
- Thermotaxis behavior of Caenorhabditis elegans is robust and highly plastic. A pair of sensory neurons, AFD, memorize environmental/cultivation temperature and communicate with a downstream neural circuit to adjust the temperature preference of the animal. This results in a behavioral bias where worms will move toward their cultivation temperature on a thermal gradient. Thermotaxis of C. elegans is also affected by the internal state and is temporarily abolished when worms are starved. Here I will discuss how C. elegans is able to modulate its behavior based on temperature by integrating environmental and internal information. Recent studies show that some parasitic nematodes have a similar thermosensory mechanism to C. elegans and exhibit cultivation-temperature-dependent thermotaxis. I will also discuss the common neural mechanisms that regulate thermosensation and thermotaxis in C. elegans and Strongyloides stercoralis.Elsevier {BV}, Jun. 2022, Current Opinion in Neurobiology, 74, 102541 - 102541, English, International magazine[Refereed][Invited]Scientific journal
- Sep. 2021, J of Cell Sci.&Ther.Insulin Signaling Acts Extensively in C. elegans Starvation-Associated Learning and Behavioral Plasticity[Refereed][Invited]
- Degenerate networks can drive similar circuit outputs. Via acute manipulation of individual neurons, we previously identified circuit components that are necessary and sufficient to drive starvation-dependent plasticity in C. elegans thermotaxis behavior. Here we find that when these components are instead silenced chronically, degenerate mechanisms compensate to drive this behavior. Our results indicate that degeneracy in neuronal network function can be revealed under specific experimental conditions.Lead, Jan. 2021, microPublication biology, 2021, English, International magazine[Refereed]Scientific journal
- Internal state alters sensory behaviors to optimize survival strategies. The neuronal mechanisms underlying hunger-dependent behavioral plasticity are not fully characterized. Here we show that feeding state alters C. elegans thermotaxis behavior by engaging a modulatory circuit whose activity gates the output of the core thermotaxis network. Feeding state does not alter the activity of the core thermotaxis circuit comprised of AFD thermosensory and AIY interneurons. Instead, prolonged food deprivation potentiates temperature responses in the AWC sensory neurons, which inhibit the postsynaptic AIA interneurons to override and disrupt AFD-driven thermotaxis behavior. Acute inhibition and activation of AWC and AIA, respectively, restores negative thermotaxis in starved animals. We find that state-dependent modulation of AWC-AIA temperature responses requires INS-1 insulin-like peptide signaling from the gut and DAF-16/FOXO function in AWC. Our results describe a mechanism by which functional reconfiguration of a sensory network via gut-brain signaling drives state-dependent behavioral flexibility.{eLife} Sciences Publications, Ltd, Oct. 2020, eLife, 9, English, International magazine[Refereed]Scientific journal
- Lead, 2020, Journal of neurogenetics, 34(3-4) (3-4), 351 - 362, English, International magazine[Refereed][Invited]Scientific journal
- Thermosensation is critical for optimal regulation of physiology and behavior. C. elegans acclimates to its cultivation temperature (Tc) and exhibits thermosensitive behaviors at temperatures relative to Tc. These behaviors are mediated primarily by the AFD sensory neurons, which are extraordinarily thermosensitive and respond to thermal fluctuations at temperatures above a Tc-determined threshold. Although cGMP signaling is necessary for thermotransduction, the thermosensors in AFD are unknown. We show that AFD-specific receptor guanylyl cyclases (rGCs) are instructive for thermosensation. In addition to being necessary for thermotransduction, ectopic expression of these rGCs confers highly temperature-dependent responses onto diverse cell types. We find that the temperature response threshold is determined by the rGC and cellular context, and that multiple domains contribute to their thermosensory properties. Identification of thermosensory rGCs in C. elegans provides insight into mechanisms of thermosensation and thermal acclimation and suggests that rGCs may represent a new family of molecular thermosensors.Lead, Apr. 2016, Neuron, 90(2) (2), 235 - 44, English, International magazine[Refereed]Scientific journal
- Information about nutrient availability is assessed via largely unknown mechanisms to drive developmental decisions, including the choice of Caenorhabditis elegans larvae to enter into the reproductive cycle or the dauer stage. In this study, we show that CMK-1 CaMKI regulates the dauer decision as a function of feeding state. CMK-1 acts cell-autonomously in the ASI, and non cell-autonomously in the AWC, sensory neurons to regulate expression of the growth promoting daf-7 TGF-β and daf-28 insulin-like peptide (ILP) genes, respectively. Feeding state regulates dynamic subcellular localization of CMK-1, and CMK-1-dependent expression of anti-dauer ILP genes, in AWC. A food-regulated balance between anti-dauer ILP signals from AWC and pro-dauer signals regulates neuroendocrine signaling and dauer entry; disruption of this balance in cmk-1 mutants drives inappropriate dauer formation under well-fed conditions. These results identify mechanisms by which nutrient information is integrated in a small neuronal network to modulate neuroendocrine signaling and developmental plasticity.Sep. 2015, eLife, 4, English, International magazine[Refereed]Scientific journal
- Sterile inflammation triggered by endogenous factors is thought to contribute to the pathogenesis of acute and chronic inflammatory diseases. Here, we demonstrate that apoptosis-deficient mutants spontaneously develop a necrosis-driven systemic immune response in Drosophila and provide an in vivo model for studying the organismal response to sterile inflammation. Metabolomic analysis of hemolymph from apoptosis-deficient mutants revealed increased sarcosine and reduced S-adenosyl-methionine (SAM) levels due to glycine N-methyltransferase (Gnmt) upregulation. We showed that Gnmt was elevated in response to Toll activation induced by the local necrosis of wing epidermal cells. Necrosis-driven inflammatory conditions induced dFoxO hyperactivation, leading to an energy-wasting phenotype. Gnmt was cell-autonomously upregulated by dFoxO in the fat body as a possible rheostat for controlling energy loss, which functioned during fasting as well as inflammatory conditions. We propose that the dFoxO-Gnmt axis is essential for the maintenance of organismal SAM metabolism and energy homeostasis.May 2014, Cell reports, 7(3) (3), 821 - 33, English, International magazine[Refereed]Scientific journal
- Effective defense responses involve the entire organism. To maintain body homeostasis after tissue damage, a systemic wound response is induced in which the response of each tissue is tightly orchestrated to avoid incomplete recovery or an excessive, damaging response. Here, we provide evidence that in the systemic response to wounding, an apoptotic caspase pathway is activated downstream of reactive oxygen species in the midgut enterocytes (ECs), cells distant from the wound site, in Drosophila. We show that a caspase-pathway mutant has defects in homeostatic gut cell renewal and that inhibiting caspase activity in fly ECs results in the production of systemic lethal factors after wounding. Our results indicate that wounding remotely controls caspase activity in ECs, which activates the tissue stem cell regeneration pathway in the gut to dampen the dangerous systemic wound reaction.Lead, Mar. 2013, Cell reports, 3(3) (3), 919 - 30, English, International magazine[Refereed]Scientific journal
- We identified a rhodol bearing a hydroxymethyl group (HMDER) as a suitable scaffold for designing fluorescence probes for various hydrolases. HMDER shows strong fluorescence at physiological pH, but phenolic O-alkylation of HMDER results in a strong preference for the spirocyclic form, which has weak fluorescence. As a proof of concept, we utilized this finding to develop a new fluorescence probe for β-galactosidase. This probe has favorable characteristics for imaging in biological samples: it has good cellular permeability, and its hydrolysis product is well-retained intracellularly. It could rapidly and clearly visualize β-galactosidase activity in cultured cells and in Drosophila melanogaster tissue, which has rarely been achieved with previously reported fluorescence probes.Aug. 2011, Journal of the American Chemical Society, 133(33) (33), 12960 - 3, English, International magazine[Refereed]Scientific journal
- Lead, Feb. 2008, DRUG DISCOVERIES AND THERAPEUTICS, 2(1) (1), 14 - 23, EnglishSensing and reacting to dangers by caspases: Caspase activation via inflammasomes[Refereed]
- Last, [豊中] : 日本比較生理生化学会, Aug. 2024, 比較生理生化学 = Comparative physiology and biochemistry / 日本比較生理生化学会 編, 41(2) (2), 84 - 90, Japanese動物の重力感知メカニズムとその役割—Mechanisms of gravity perception and their roles in animals[Refereed]Introduction scientific journal
- 2022, 日本神経化学会大会抄録集(Web), 65th線虫C.エレガンスにおける温度情報および匂い刺激の統合を調節する責任遺伝子のスクリーニング
- Joint work, 朝倉書店, Jun. 2025, Japanese, ISBN: 9784254171891生き物と匂い・フェロモンの事典Dictionary or encycropedia
- Joint editor, 文研出版, Aug. 2021, ISBN: 4580824660五感と運動のふしぎ
- Contributor, 線虫の温度受容体としてのグアニル酸シクラーゼ, 羊土社, Sep. 2016, Japanese, ISBN: 9784758101554「特集」発がん : 遺伝子変異+αの真実に迫る
- ニュートリオミクスフォーラム2025, Mar. 2025, Japanese, Domestic conference線虫における生育可能温度の制御メカニズムの解明[Invited]Invited oral presentation
- RIKEN Hakubi-ECL symposium 2025, Jan. 2025, English, Domestic conferenceMechanisms that animals process sensory information[Invited]Invited oral presentation
- 日本動物学会 第95回長崎大会 2024, Sep. 2024, Japanese, Domestic conference線虫が多感覚情報を統合して行動を決定する神経・分子メカニズムの解明[Invited]Invited oral presentation
- nFuture2024, Aug. 2024, English, Domestic conferenceIdentification of the genes that regulate heat-tolerance in C. elegansPoster presentation
- nFuture2024, Aug. 2024, English, Domestic conferenceIdentifying novel genes involved in the integration of temperature and odor information in C. elegans through an unbiased genetic screenPoster presentation
- C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior (CeNeuro) (2024) Madison Poster presentation, Jun. 2024, English, International conferenceScreening of novel genes involved in the integration of the temperature and odor information in C. elegansPoster presentation
- Asia-Pacific Worm meeting 2024, Jun. 2024, English, International conferenceIdentification of the genes that regulate heat-tolerance in C. elegans[Invited]Invited oral presentation
- Evident Creative Forum 2024, Feb. 2024, Japanese, Domestic conferenceInvestigation of neural mechanism that mediates temperature dependent behavior in C. elegans[Invited]Public discourse
- The 46th Annual Meeting of the Japan Neuroscience Society, Aug. 2023, Japanese, International conferenceGenetic analysis of neural basis that governs behavior in C. elegans[Invited]Invited oral presentation
- The 46th Annual Meeting of the Japan Neuroscience Society, Aug. 2023, English, International conferenceMolecular analysis of odor and temperature sensory integration in C. elegans[Invited]Nominated symposium
- NPBR 線虫講習会, Dec. 2022NBRP 線虫講習会[Invited]Public discourse
- The 43th Annual Meeting of the Molecular Biology Society of Japan, Dec. 2020Neuronal mechanisms that drive starvation-dependent thermotaxis plasticity in C. elegans[Invited]Nominated symposium
- 第12会若手インスパイアシンポジウム, 2020線虫を用いた行動決定メカニズムの解明[Invited]Nominated symposium
- NSI workshop 2019, 2019Neural Communication that Mediates Starvation-dependent Thermotaxis Plasticity in C. elegan[Invited]Public symposium
- CeNeuro 2018, Jul. 2018Molecular and neuronal mechanisms mediating starvation-dependent thermosensory behavioral plasticityPoster presentation
- 21st International C. elegans Meeting, Jul. 2017Molecular and neuronal mechanisms underlying feeding state-dependent plasticity in thermotaxis behaviorsPoster presentation
- CeNeuro2016, Jun. 2016AFD-specific receptor guanylyl cyclases confer thermosensory responsesOral presentation
- CeNeuro2016, Jun. 2016Molecular and neuronal mechanisms of feeding state-dependent thermotaxis behavioral plasticityPoster presentation
- 20th International C. elegans Meeting, Jun. 2015AFD-specific receptor guanylyl cyclases can confer temperature responses onto diverse cell typesOral presentation
- CeNeuro 2014, Jul. 2014The AWC and ASI sensory neurons contribute to starvation-dependent plasticity in thermotaxis behaviorPoster presentation
- Drosophila Research conference 10, Oct. 2012Gut cell turnover via caspase mediates systemic wound responsePoster presentation
- New Frontiers of Metabolism Research in Biomedical Sciences, Sep. 2012Regulation of systemic wound response via caspase activity in gutPoster presentation
- 2012 Drosophila Research Conference, Mar. 2012Caspase activity in gut mediates systemic response against tissue damageOral presentation
- The Tissue Repair & Regeneration Gordon-Kenan Research Seminar, Jun. 2011The regulation of systemic response via caspase pathway to overcome tissue damag[Invited]Invited oral presentation
- 13th international TNF conference, May 2011Genetic analysis of the cell death signal in the response against tissue injuryPoster presentation
- Homeostatic inflammation Workshop for Young Scientists, Jan. 2011Injury Induced Defense Mechanism via caspaseOral presentation
- 21st European Drosophila Research Conference, Nov. 2009Genetic dissection of tissue injury-induced cell death-related signaling in DrosophilaPoster presentation
- Drosophila Research Conference 9, Jul. 2009Genetic Analysis of Defense Mechanisms against Tissue InjuryPoster presentation
- The 82nd Annual Meeting of the Japanese Biochemical Society, May 2009Involvement of caspase pathway in the response against tissue injuryOral presentation
- The 15th Takeda Science Foundation Symposium on Bioscience, Dec. 2008In vivo dynamics of caspase activation in Drosophila during host defensePoster presentation
- The 8th Awaji International Forum on Infection and Immunity, Sep. 2008Analysis of Caspase activation in Drosophila during host defenseOral presentation
- The 7st International Cell Death Society Symposium, Jun. 2008Live Imaging of the Caspase Activity during the Wound HealingPoster presentation
- The 8th Meeting of Japanese Drosophila Research Conference, Jul. 2007Live Imaging of the Caspase Activity during the Wound HealingPoster presentation
- 日本動物学会2024 - Present
- 日本神経科学会2022 - Present
- 日本分子生物学会2020 - Present
- The Genetics Society of America2015 - 2019
- 日本生化学会2009 - 2012
- 国立研究開発法人科学技術振興機構, CREST, 大学共同利用機関法人自然科学研究機構 生理学研究所, Oct. 2024 - Mar. 2030VR多次元環境における生存戦略の脳回路動態解明
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 国立研究開発法人理化学研究所, 01 Apr. 2022 - 31 Mar. 2025線虫におけるゲノム、エピゲノム変化を介した温度適応機構の解明
- 日本学術振興会, 科学研究費助成事業 国際共同研究加速基金(国際共同研究強化(B)), 国際共同研究加速基金(国際共同研究強化(B)), 名古屋市立大学, Oct. 2022 - Mar. 2025, Coinvestigator自動追跡ロボット技術と超高速三次元イメージング技術の統合による脳動作原理の解明
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, Institute of Physical and Chemical Research, 01 Apr. 2020 - 31 Mar. 2022Investigation of neural mechanisms that mediates behavior decision under multiple environmental stimuli in C. elegansIn order to investigate how brain processes multiple information, we used the model animal C. elegans and examined how it makes behavioral decisions when it is exposed to multiple environmental stimuli. Specifically, we conducted behavior assays and calcium imaging assays on single neurons on the worms that are exposed to temperature and odor stimuli simultaneously. Our results show that C. elegans prioritizes different environmental cue depending on the circumstance of the animal. We succeeded to identify couple candidate gene that are involved in the integration of odor and temperature stimuli.
- 日本学術振興会, 科学研究費助成事業 特別研究員奨励費, 特別研究員奨励費, 東京大学, 2009 - 2011組織傷害により誘導される生体ストレス因子の同定とその制御機構の解明ダメージを受けた個体では、その情報を伝えるdanger signalが正常細胞へ伝播され、生体防御機構を活性化するという概念が確立されたが、どのようなdanger signalが、個体や組織に対してどのような影響を与えているのかは未だ不明である。これまでの研究成果から、損傷後の生存には腸におけるカスパーゼの活性化が必要であること、表皮の損傷後30分以内に腸のEC(吸収細胞)においてカスパーゼの活性化が認められ、ECが細胞死を引き起こすことを見出した。また、dpf-1変異体では損傷後の体液中に致死性誘導因子が存在することを示し、野生型とdpf-1変異体において損傷を与えた場合と与えていない場合の体液のプロテオミクス解析、メタボロミクス解析を行った。 本年度はまず、電子顕微鏡観察により、dpf-1変異体の腸を取り巻く筋肉細胞やECMに以上があることを示した。また、野生型の腸におけるカスパーゼの活性化ECが腸管内腔側に突出し、核膜の構造が不明瞭になる様子が観察され、損傷後に腸細胞が脱落する様子をより詳細に解析した。さらに、dpf-1変異体で腸のECの入れ替わりに異常があることを示すため、一過的にECのみにプローブを発現させたハエを6日後に解剖することにより、プローブを発現した細胞がどの程度入れ替わったかを調べる実験を行った。その結果、野生型では6日間で40%程度のECが入れ替わったのに対し、dpf-1変異体では入れ替わったECは10%以下であった。このECの入れ替わりの阻害が損傷後の生存にどのように影響するかを検証するため、ISC(腸幹細胞)の細胞増殖を抑制し、新たなECの産生が抑制されたショウジョウバエを用いて表皮の損傷後の生存率を調べる実験を行ったところ、生存率の低下が認められた。さらに、プロテオミクス解析で得た致死性誘導因子の候補分子の一つ、カテプシン様タンパク質がdpf-1の損傷後の生存率の低下に寄与している可能性を示すデータを得た。
- Lecturer, 28 Jul. 2024第36回 愛媛新聞小学生読書感想文コンクール、小学生向けの実験ワークショップ
- Lecturer, Nov. 2022Science class
- Lecturer, Jul. 2021 - Jul. 2021Summer program for high school students
- Communications Biology, External Editorial Board memberCommunications Biology, External Editorial Board member01 Oct. 2020 - Present
- CeNeuroCeNeuro24 Jun. 2024 - 26 Jun. 2024
- nFuturenFutureAug. 2021Academic society etc
- 23rd International C. elegans conference23rd International C. elegans conference2021Academic society etc
