NEWS

2019.9
New paper in Nature Communications
Comparative genomics reveals the origin of fungal hyphae and multicellularity.
Kiss E, Hegedüs B, Virágh M, Varga T, Merényi Z, Kószó T, Bálint B, Prasanna AN, Krizsán K, Kocsubé S, Riquelme M, Takeshita N, Nagy LG.

Press release, Japanese
https://www.jst.go.jp/pr/info/info1390/index.html

2019.9
New paper in Anal Chem, Fungal Cells by Raman Hyperspectral Imaging
Inhomogeneous Molecular Distributions and Cytochrome Types and Redox States in Fungal Cells Revealed by Raman Hyperspectral Imaging Using Multivariate Curve Resolution-Alternating Least Squares.
Yasuda M, Takeshita N, Shigeto S.

2019.6
Visited Karlsruhe Institute of Technology (KIT), Institut Pasteur (Paris), Gerog-August-University Goettingen, and Max Planck Institute for terrestrial microbiology (Marburg) by JST lectureship .

2019.4
Topics Award in JSBBA (Japan Society for Bioscience, Biotechnology and Agrochemistry) annual meeting at Tokyo for Momoka Kuchira and Mizuki Yasui
https://jsbba.bioweb.ne.jp/jsbba2019/index.php?btn2_move=on&topics=1

2019.4
Awarded Ohsumi Frontier Science Foundation
https://www.ofsf.or.jp/activity/02_result.html

2019.3
Attended to 30th Fungal Genetics Conference
Asilomar, CA, USA
http://conferences.genetics-gsa.org/Fungal/2019/index .

2018.11
18th Fungal Genetics and Molecular Biology Conference
Nagaoka, Japan
Best Poster Award for Momoka Kuchira and Sayumi Fukuda
Industry Poster Award for Mizuki Yasui

2018.9
TGSW2018, Tsukuba Global Science Week, Tsukuba
Towards Microbial Control ver. 3.0
Best Poster Award for Gayan Dakshitha and Sayumi Fukuda
Excellent Poster Award for Tomoko Serizawa

2018.9
Symposium at
82nd Annual Meeting of the Botanical Society of Japan 植物学会, Hiroshima

22nd Yeast symposium 酵母合同シンポ, Fukuoka

70th Annual meeting of the Society for Biotechnology 生物工学会, Osaka

2018.8
Gram-positive bacterium genome function conference, Atami
Excellent Poster Award for Momoka Kuchira

2018.4
New review in Microbiol Mol Biol Reviews
Fungal Morphogenesis, from the Polarized Growth of Hyphae to Complex Reproduction and Infection Structures
Riquelme M, Aguirre J, Bartnicki-García S, Braus GH, Feldbrügge M, Fleig U, Hansberg W, Herrera-Estrella A, Kämper J, Kück U, Mouriño-Pérez RR, Takeshita N, Fischer R

2018.3
Attended to 14th ECFG
Haifa, Israel
http://www.ecfg14.org .

2018.1
New paper in Science Advances
Superresolution and pulse-chase imaging reveal the role of vesicle transport in polar growth of fungal cells.
Zhou L, Evangelinos M, Wernet V, Eckert A, Ishitsuka Y, Fischer R, Nienhaus GU, Takeshita N

Press release
http://www.tsukuba.ac.jp/en/research-list/p201801250910
[Japanese]
http://www.tsukuba.ac.jp/attention-research/p201801250400.html
http://www.jst.go.jp/pr/announce/20180125-2/index.html .

2018.1
New review in Fung Genet Biol
Oscillatory fungal cell growth.
Takeshita N

2017.12
Attended to ConBio2017
Kobe, Japan
http://www2.aeplan.co.jp/conbio2017/english/

2017.11
Attended to 17th Fungal Genetics and Molecular Biology Conference
Saga, Japan　　糸状菌分子生物学コンファレンス
http://www.biosci.osakafu-u.ac.jp/fmbsj/english/

2017.11
16th Workshop of MIcrobiology
Tokyo Institute of Technology
Poster Award; Momoka Kuchira
http://www.res.titech.ac.jp/~biores/cn20/BIKEN.html

2017.10
Gave a lecture at Max Planck Institute for Terrestrial Microbiology
Marburg, Germany

.

2017.10
Visited Karlsruhe for the first time in a year
Germany

.

2017.08
Attended to XII International Fungal Biology Conference
Incheon, South Korea
http://ifbc2017.org/register/2017_01/main.html .

2017.08
New paper in Mol Microbiol
Microtubule-organizing centers of Aspergillus nidulans are anchored at septa by a disordered protein.
Zhang Y, Gao X, Manck R, Schmid M, Osmani AH, Osmani SA, Takeshita N, Fischer R.

2017.06.18
Commentary on newspaper Nikkei,　日本経済新聞
http://www.nikkei.com/article/DGKKZO17751630W7A610C1MY1000/

2017.06
Awarded Japan Society For Molecular Biology of Filamentous Fungi Award for Young Scientists,　糸状菌遺伝子研究会奨励賞
http://fungi.mysterious.jp/MAIN-J/News.html

2017. 05
Press release of the new publication in PNAS.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=175296&CultureCode=en
[Japanese]
http://www.jst.go.jp/pr/announce/20170516-2/index.html
https://www.tsukuba.ac.jp/attention-research/p201705160400b.html

201705New publication inPNAS.

2017.03
Awarded JSBBA (Japan Society for Bioscience, Biotechnology and Agrochemistry) Award for Young Scientists,　日本農芸化学会奨励賞
http://www.jsbba.or.jp/about/awards/about_awards_encouragement.html 201703日本農芸化学会奨励賞

JAPANESE

Research

MOLD; FILAMENTOUS FUNGI

Mold is a microorganism that is widespread in the natural environment. Interestingly, by continuous growth of filamentous cells (mycelium), mold has developed into the largest creature identified on earth in Oregon, covering 965 hectares. Molds are believed to provide the largest variety and the largest volume of microbes in the soil. Fungi secrete a lot of enzymes and decompose organic matter during growth. This decomposer function is essential for materials circulation of ecosystem. For a long time, humans have made use of filamentous fungi in the production of fermented foods (sake, soy sauce, blue cheese, etc.) and, more recently, for the production of many useful enzymes and antibiotics in biotechnology. However, some fungal species can invade immunocompromised humans and agricultural crops, causing serious damage. Fungal pathogenicity is indeed a major problem in the medical and agricultural fields.

Our group analyzes the molecular mechanisms of mycelial elongation, the key process underlying both the usefulness and pathogenicity of mold. Filamentous fungi continuously extend the cell body at one end of their hyphae in a process called “tip growth”. Polar tip growth requires continuous transport of construction materials to and away from the hyphal tip. Proteins and other biomolecules are packaged in massive vesicles and transported over long distances by motor proteins along the actin and microtubule cytoskeletons.

Cell end marker

Why polarity?

Cell polarity is essential for the proper function of many cell types, because the cell function is optimized by the cell shape, and the cell shape is determined by the cell polarity. Filamentous fungi grow by tip-extension. The mode of growth depends on stable polarity at the hyphal tip. How is the polarity regulated in filamentous fungi?
Why do filamentous fungi grow filamentous?

Cell end marker

Cell end markes

We found landmark proteins named “cell end markers”, which control the polarity. The cell end markers, TeaA and TeaR, localize at hyphal tips interdependently. TeaA is delivered to hyphal tips by growing microtubules (MTs), anchored to the hyphal tip cortex though the interaction with TeaR, membrane associated TeaA receptor. TeaA at the tip indirectly interacts with the formin SepA which forms actin cables that are required for secretion vesicle transport and polarized growth. The teaA and teaR deletion mutants showed defects in polarity maintenance, which lead to curved or zig-zag growing hyphae. Thus TeaA transmits positional information regulated by MTs to the actin cytoskeleton at hyphal tips. The mechanism is required for the polarity maintenance and the growth direction of hyphae.

MT and plasma membrane

The interaction between MT plus end and the plasma membrane is important for the establishment and maintenance of polarity. MT plus-end localizing proteins (+TIPs) regulate MT plus-end dynamics. AlpA, a XMAP215 family protein and one of +TIPs, promotes MT growth and functions as MT polymerase. The functional connection between the cell end marker TeaA at the plasma membrane and AlpA at MT plus-ends is important for the proper regulation of MT growth at hyphal tips. In this way, we focus on the connection among MT plus ends, plasma membrane and actin cytoskeleton for polarized growth.

Cell end marker

Visualization of membrane domains by super-resolution microscopy

Apical sterol-rich membrane domains (SRDs) are gaining attention for their important roles in polarized growth of filamentous fungi, however their exact figure, roles and formation mechanisms remain rather unclear. We selected genes involved in membrane recycle, raft formation and lipid transport, etc. We are investigating their roles of on the formation and maintenance of SRD and their interplay with the cytoskeletons.
The SRDs are revealed to be a mixture of lipid raft and non-raft microdomains, however the size of rafts is ranging between 10 and 200 nm and is thus too small to detect by conventional light microscopy which has a resolution limit of 250 nm. In recent years, super-resolution microscope techniques have been improving and breaking the diffraction limit of conventional light microscopy. One of the techniques is photoactivation localization microscopy (PALM) using photoswitchable (or photoactivatable) fluorophores. The lateral image resolution as high as 20 nm which can be acquired via this method will be a powerful tool to investigate the relation of lipid membrane domains and protein localization in living cells deeply. Size, number, distribution and dynamics of membrane domains, and dynamics of single molecules are subjects of our research. Additionally we are investing the MT and actin cytoskeleton, and their relation with membrane domains.

Cell end marker

ENGLISH

Research

約38億年前に微生物が誕生しました。 現在、地球上に多くの生物が存在するのも、微生物が大きな地球環境の変動に適応し、進化と活動を続けてきた結果であると言えます。このような多様な微生物は地球上の至る所に存在し、我々の生活にも深く関与しています。我々の体内にいる微生物、農業・食に関与する微生物、我々をとりまく様々な環境にいる微生物、それらが我々の健康や食料、そして地球環境に深く関与しています。近年、それら多様な微生物群が他者（微生物、植物、動物など）と複雑でしなやかな相互作用を及ぼすことで、様々な機能を発揮することが明らかになってきています。

糸状菌（菌類、カビやキノコ、真菌）

菌類は一般に、キノコやカビのように菌糸や子実体（胞子形成のために作る複合的な構造）を形成する生活環を持つ糸状菌、酵母と呼ばれる単細胞性の生活環を持つ菌などの真核生物の総称です。真核生物が誕生して27億年と予想されていますが、菌類は生物界では動物界、植物界に並ぶ菌界に分類され、200-500万種も存在すると試算される巨大な生物群です。菌類にはさまざまな分類群が含まれ、非常に大きな形態的・生物学的多様性を示します。糸状菌は菌糸と呼ばれる細胞を伸ばし成長する微生物ですが、その菌糸を伸ばし続けた多細胞性のネットワークは、地球上の最大の生き物にもなります（注1）。ある程度菌糸を伸ばすと胞子を作り、胞子の散布により異なる環境で再び菌糸を伸ばし増殖を始めます。外部の有機物を利用する従属栄養生物であり、分解酵素を分泌して細胞外で養分を消化し、細胞表面から摂取します。
　菌糸の伸長と分岐からなる多細胞性の菌糸体は、糸状菌の大きな特徴で、その養分吸収や病原性などに関わります。自然界では分解者として重要な役割を果たしており、生態系の物質循環に欠かせない存在です。特に土壌中では、糸状菌は最大体積の生き物であると考えられています。糸状菌は伸びる際に多くの酵素を出し有機物を分解します。その分解者としての役割は生態系の物質循環を制御しています。
　糸状菌の中には、コウジカビのように伝統的な発酵食品（酒・醤油・味噌など）の生産に関わるものが、あります。近年では、様々な化合物（クエン酸、イタコン酸など）の生産に利用され、飲料食品や化学合成繊維・樹脂といったバイオ産業で利用されています。食品・飼料・洗剤工場などでは、糸状菌に作らせた様々な酵素を利用しています。植物系バイオマスを分解することでバイオエタノールの生産に関わるものなどもあります。このように糸状菌を利用した製品は、年間3000億円市場と言われており、私たちは知らないうちに（？）その恩恵を受けています。
　一方で、免疫不全の人間に侵入し病原性を示す真菌症は、治療が困難で医学分野で大きな問題となっています。真菌（糸状菌、酵母）も人間と同じ真核生物であるため、副作用の低い治療薬が少ないのが現状です。また、植物病原菌の約80%が糸状菌であり、農作物の10%が毎年失われていると言われています。一方で、植物の根に接触し共生する菌（内生菌、菌根菌）は、土壌からリンや窒素源を植物に供給し、代わりに植物が光合成で生産した炭素のエネルギー源を得ることで生育します。これらの糸状菌は、植物が陸上に進出する際に植物を助けたと考えられており、植物の約80%が糸状菌と相互作用しています。
　環境中で全ての生物が、他者と関わりあいながら生きています。糸状菌は他の細菌、糸状菌、虫、植物、動物と関わりあいながら、時に助け合い、時に戦いながら、共生と寄生を柔軟に選択して生きています。そこでコミュニケーションするための化合物として、ペニシリンのような抗生物質や医薬品の元となる生理活性物質（免疫抑制剤、抗がん剤、コレステロール低下剤；注2）を生産します。冬虫夏草などの漢方として古くから利用されているものもありますが、まだまだ未知の化合物が残されています。 　 　

私たちのグループでは、このような糸状菌の特性（有用性と病原性）をもたらす菌糸が伸びる分子機構を研究しています。また、糸状菌と他の生物（細菌、植物など）との相互作用について研究し、生態系での役割を明らかにしようとしています。

最新のテクノロジーで、最高のサイエンスに挑戦し、世界に発信します。

菌糸が伸びる仕組み

https://www.jstage.jst.go.jp/article/kagakutoseibutsu/51/12/51_809/_pdf



（注1）世界最大の生き物は菌類；　1998年にアメリカ、オレゴン州の東部で発見されたキシメジ科のキノコ、オニナラタケ(Armillaria ostoyae)の菌床は、総面積8.9平方キロメートルに及び、推定重量はおよそ600t、推定年齢は約2400歳といわれています。キノコもカビの仲間で、土や木の中に菌糸を作り生長します。地表に出ている胞子を作る器官（子実体）が、キノコと呼ばれるものです。
（注2）スタチン；コレステロール合成に関わる酵素の阻害剤で、Pfizer社のリピトールは世界で最も売れている薬で、2008年の売上高は1兆2000億円です。

Publications

Selected publications (Corresponding author *)

Review



Complete publication list

https://www.ncbi.nlm.nih.gov/pubmed/?term=norio+takeshita

Research Gate

https://www.researchgate.net/profile/Norio_Takeshita



Books

  • Takeshita N, Fischer R.
    The cytoskeleton and cell-end markers during polarized growth of filamentous fungi.
    Mycota VII 3rd edition, Springer (2018)
  • Etxebeste O, Takeshita N.
    Advanced microscopy methods for the study of protein localization, interaction and dynamics in filamentous fungi.
    Advanced Microscopy in Mycology, Springer (2015)
  • Fischer R, Takeshita N, Doonan J.
    Cytoskeleton, Polarized Growth, and the Cell Cycle in Aspergillus nidulans.
    The Aspegilli: Genomics, Medical Applications, Biotechnology, and Research Methods (2007)

About

筑波大学へNorio Takeshita

Norio Takeshita PhD

University of Tsukuba
Faculty of Life and Environmental Sciences
Microbiology Research Center for Sustainability (MiCS)
e-mail: takeshita.norio.gf@u.tsukuba.ac.jp

Career

2019.4 -
Associate Professor
University of Tsukuba
Faculty of Life and Environmental Sciences
Microbiology Research Center for Sustainability (MiCS)

2014.7 - 2019.3
International Tenure Assistant Professor
University of Tsukuba
Faculty of Life and Environmental Sciences

2016.10 -
Group leader
JST ERATO Nomura project, Genome biochemistry group

2011.10 – 2016.9
Group leader
Karlsruhe Institute of Technology (KIT)
Applied Bioscience, Dept. Microbiology

2008.4 - 2011.9
Research Associate
Karlsruhe Institute of Technology (KIT)
Applied Bioscience, Dept. Microbiology

2006.4 - 2008.3
Postdoc fellow of Alexander von Humboldt Foundation
University of Karlsruhe
Applied Bioscience, Dept. Microbiology

Education

2003.4 - 2006.3
Ph.D.
The University of Tokyo
Graduate school of agricultural and life science, Dept. Biotechnology

2001.4 - 2003.3
Master
The University of Tokyo
Graduate school of agricultural and life science, Dept. Biotechnology

1997.4 - 2001.3
Bachelor
The University of Tokyo, Faculty of agriculture, Dept. Biotechnology



Funding

DFG, Landesstiftung Baden Württemberg, Humboldt Society
JSPS, JST



Editorial board

Fungal Genetics Biology

Fungal Biology Biotechnology



Awards

2017. Japan Society For Molecular Biology of Filamentous Fungi Award for Young Scientists (糸状菌遺伝子研究会奨励賞)

2017. JSBBA Award for Young Scientists (日本農芸化学会奨励賞)

2012. Elite program member of Baden-Wurttemberg Foundation



Fellowship

2006 - 2008
Fellowship of the Alexander von Humboldt Foundation

2004 - 2006
Research Fellowships of Japan Society for the Dissertation of Science (JSPS) for Young Scientists (DC2)



Oral presentation at international conference

2019, Oct Asia Mycology Conference, Tsu, Japan
2019, Mar 30th Fungal Genetics Conference, Asilomar, USA
2018, Mar 14th Europian Conference on Fungal Genetics, Haifa, Israel
2017, Aug XII International Fungal Biology Conference, Incheon, South Korea
2016, Apr 13th Europian Conference on Fungal Genetics, Paris, France
2016, Mar VAAM annual congress, Jena, Germany
2015, Oct Molecular Biology of Fungi, Berlin, Germany
2015, Sept Membrane Compartmentalization, Munster, Germany
2015, Mar 28th Fungal Genetics Conference, Asilomar, USA
2014, Mar 12th Europian Conference on Fungal Genetics, Seville, Spain
2013, Oct XI International Fungal Biology Conference, Karlsruhe, Germany
2013, Mar 27th Fungal Genetics Conference, Asilomar, USA
2012, Oct Eurofung meeting 2012, Berlin, Gemany
2012, May Workshop DFG-CONACyT Research Unit 1334, Mexico city, Mexico
2012, Mar 11th European Conference on Fungal Genetics, Marburg, Germany
2011, Mar 26th Fungal Genetics Conference, Asilomar, USA
2011, Sept VAAM Symposium, Molecular Biology of Fungi, Marburg, Germany
2009, Nov Eurofung meeting 2009, Wageningen, Netherlands
2009, Mar 25th Fungal Genetics Conference, Asilomar, USA
2008, Oct Eurofung meeting, San Feliu de Guixols, Spain
2008, Mar 9th European Conference on Fungal Genetics, Edinburgh, Scottland
2007, Sept VAAM Symposium, Molecular Biology of Fungi, Hamburg, Germany
2007, May Eurofung meeting 2007, Wageningen, Netherlands
2007, Mar 24th Fungal Genetics Conference, Asilomar, USA


Invited lecture

2019, Nov Hokkaido University, Physical Ethology Lab
2019, Sep Tsukuba University at Sugadaira, Lab of Mycology
2019, Jun Max Planck Institute for terrestrial microbiology (Marburg)
2019, Jun Gerog-August-University Goettingen
2019, Jun Institut Pasteur (Paris)
2019, Jun Karlsruhe Institute of Technology (KIT)
2019, Apr RIKEN yokohama, iSYM
2019, Apr AIST, National Institute of Advanced Industrial Science and Technology
2018, Apr Agricultural and Life Science, The University of Tokyo
2017, Dec Faculty of Agriculture, Yamaguchi University
2017, Nov Faculty of Agriculture, Kyushu University
2017, Oct Max Planck Institute for Terrestrial Microbiology, Marburg
2017, Jul ITbM, Nagoya University
2016, Jan Agricultural and Life Science, The University of Tokyo
2015, Nov Faculty of Life and Environmental Sciences, University of Tsukuba
2015, Oct Institute of Applied Physics, Karlsruhe Institute of Technology
2015, Sept Cell Networks-Cluster of Excellence and Centre, University of Heidelberg
2015, Jan Institute for Microbiology and Genetics, Georg August University of Goettingen
2014, Nov Faculty of Agriculture, Kyoto University
2014, Nov Faculty of Agriculture, Tohoku University
2014, Apr Kyoto Prefectural University
2014, Apr National Research Institute of Brewing
2013, Dec Bioagricultural and Life Sciences, Nagoya University
2013, Dec Agricultural and Life Science, The University of Tokyo
2013, Mar Stanford University School of Medicine
2013, Mar Max Planck Institute of Molecular Cell Biology and Genetics, Dresden

Symposium at domestic conference

2019, 11　東工大 酵素工学研究会　　
第82回講演会
2019, 7　東京 微生物ウィーク2019　　
令和新時代における糸状菌・酵母研究の挑戦
2019, 5　秋田 日本菌学会　　
菌類の進化と共生と成長ダイナミクス
2018, 9　広島 日本植物学会　　
細胞の極性成長を支える分子メカニズムの共通性と独自性
2018, 9　九州大 酵母合同シンポジウム　　
アジアへのゲートウェイ九州から発信する酵母の魅力
2018, 9　関西大 日本生物工学会　　
真核微生物におけるシグナル伝達と代謝の接点を探る
2018, 6　東農大 醤油研究発表会　　
蛍光ライブイメージングで「観る」糸状菌の菌糸生長
2018, 3　名古屋 農芸化学会2018　　
先進解析技術が拓く糸状菌研究
2017, 12　東大 第3回関東支部例会　　
微生物･植物の機能とメカニズムに迫る
2017, 11　佐賀 第17回糸状菌分子生物学コンファレンス　　
糸状菌の特徴解明の最前線：基礎から病原性，産業利用まで

Members

M2 Tomoko Serizawa s1821113[at]s.tsukuba.ac.jp Tip growth & calcium signal
M2 Momoka Kuchira s1821097[at]s.tsukuba.ac.jp Fungal-bacterial interaction
M2 Mizuki Yasui s1821158[at]s.tsukuba.ac.jp Fungal growth into steamed rice
M2 Gayan Dakshitha s1830197[at]s.tsukuba.ac.jp Screening of antibiotics
M1 Sayumi Fukuda s1510718[at]u.tsukuba.ac.jp Super resolution imaging & microfluidic device
B4 Gamon Kudo s1610664[at]u.tsukuba.ac.jp Ecological microbe interaction

JAPANESE

Contact

Norio Takeshita PhD

University of Tsukuba, Faculty of Life and Environmental Sciences,
Laboratory of Advanced Research A, 515
Tennodai 1-1-1, Tsukuba, 305-8572, Japan.
Tel: +81-29-853-6782 / 7191
e-mail: takeshita.norio.gf@u.tsukuba.ac.jp

Highly motivated and productive postgraduate research candidates are welcome to work with us. Email a statement of your research interest with your recently updated CV and academic transcript. Prospective candidates are encouraged to apply for MEXT (Monbukagakusho Japanese government scholarship) for financial support.

ENGLISH

Contact

竹下　典男

筑波大学生命環境系
305－8577
茨城県つくば市天王台1-1-1
筑波大学総合研究棟A 515
電話：029-853-6782 / 7191
e-mail: takeshita.norio.gf@u.tsukuba.ac.jp

研究グループへの参加（修士、博士、ポスドク）、共同研究、あらゆる可能性がオープンです。随時、連絡をお待ちしています。