RESEARCH SUPPORT


CONTENTS


TECHNOLOGY DEPARTMENT


Head:Hiroyuki Hattori

Common Facility Group
Chief:Kazuhiko Furukawa
Research Support Facilities
Mamoru Kubota(Subunit Chief), Chieko Nanba, Toshiki Ohkawa, Masayo Iwaki, Kaoru Sawada, Tomoki Miwa, Hideko Nonaka
Radioisotope Facility
Yousuke Kato(Subunit Chief), Yoshimi Matsuda
Center for Analytical Instruments
Akio Murakami(Unit Chief), Sonoko Ohsawa, Yukiko Kabeya, Yumiko Makino, Takeshi Mizutani
Glassware Washing Facility
(Kazuhiko Furukawa), (Toshiki Ohkawa)
Research Support Group
Cell Biology Group
Maki Kondo, Katsushi Yamaguchi
Developmental Biology Group
Hiroko Kobayashi(Unit Chief), Sachiko Fukada, Chikako Inoue, Chiyo Takagi
Regulation Biology Group
Shoichi Higashi, Miki Ida, Akiko Kawai, Shigemi Ohsugi
Gene Expression and Regulation Group
Koji Hayashi, Tomoko Mori, Yasushi Takeuchi, Hideko Utsumi

The Technology Department is a supporting organization for researchers and research organi-zation within the NIBB. The Department develops and promotes the institute's research activities and at the same time, maintains the research functions of the institute.
The Department is organized into two groups: one, the Common Facility Group, which supports and maintains the institute's common research facilities and the other, the Research Support Group, which assists the research activities as described in individual reports.
Technical staffs participate, through the depart-ment, in mutual enlightenment and education, and increase their capability in technical area. Each technical staff is proceeded to the fixed division usually and they support the various research with their special biological and biophysical techniques.
The Department hosts an annual meeting for technical engineers who work in various fields of biology at universities and research institutes throughout Japan. At this meeting, the participants present their own activities and discuss technical problems. The Proceedings are published soon after the meeting.


CONTENTS


RESEARCH SUPPORT FACILITY


Head of Facility: Mikio Nishimura
Associate Professor: Masakatsu Watanabe
Research Associates:Yoshio Hamada, (Tissue and Cell Culture), Kenta Nakai (Computer ;-April 30, 1995)
Technical Staff: Mamoru Kubota, Chieko Nanba, Toshiki Ohkawa, Kaoru Sawada, Tomoki Miwa, Hideko Nonaka, Kimiko Yamamiya (-March 31, 1995), Masayo Iwaki (June 1, 1995-)

The Facility provides large-and medium-scale instruments and facilities for biophysical, molecular biological, and computational analyses as well as for growing and maintaining biological specimens. The facility is shared among the research members, and has seven laboratories, among which the Large Spectrograph Laboratory and the Laboratory of Stress-Resistant Plants are dedicated to cooperative use under the NIBB Cooperative Research Programs.

I. Facilities

1. The Large Spectrograph Laboratory

This laboratory provides, for cooperative use, the Okazaki Large Spectrograph (OLS), which is the largest spectrograph in the world, dedicated to action spectroscopical studies of various light-controlled biological processes. The spectrograph runs on a 30 kW-Xenon arc lamp and has a compound grating composed of 36 smaller individual gratings. It projects a spectrum of a wavelength range from 250 nm (ultraviolet) to 1,000 nm (infrared) onto its focal curve of 10 m in length. The fluence rate (intensity) of the monochromatic light at each wavelength is more than twice as much as that of the corresponding monochromatic component of tropial sunlight at noon (Watanabe et al., 1982, Photochem. Photobiol., 36, 491-498). A tunable two-wavelength CW laser irradiation system is also available as a complementary light source to OLS to be used in irradiation experiments which specifically require ultra-high fluence rates as well as ultra-high spectral-, time-and spatial-resolutions. It is composed of a high-power Ar-ion laser (Coherent, Innova 20) (336.6-528.7 nm, 20 W output), two CW dye lasers (Coherent, CR599-01) (420-930 nm, 250-1000 mW output),
A/O modulators (up to 40 MHz) to chop the laser beam, a beam expander, and a tracking microbeam irradiator (up to 200 Mu ms-1 in tracking speed, down to 2Mum in beam diameter) with an infrared phase-contrast observation system.

2. Tissue and Cell Culture Laboratory

Various equipments for tissue and cell culture are provided. This laboratory is equipped with safely rooms which satisfy the P2/P3 physical containment level. This facility is routinely used for DNA recombination experiments.

3. Computer Laboratory

To meet various computational needs and to provide means of electronic communication in this Institute, many kind of computers are equipped: VAX/VMS machines, UNIX engineering workstations (SPARCstations, NEWS machines, DECstations), and some personal computers (Macintosh's and Windows machines). All of these machines are connected each other through the Ethernet, the Fast Ethernet, or the CDDI, which are also linked by optical fibers to the high performance multimedia backbone network of Okazaki National Research Institutes. Since this backbone network, called ORION, is joined to the Internet, the users of these machines can access various services and databases on the Internet. Each laboratory has several computers that are also connected to the network of the Institute. The Computer Laboratory provides various computational services to the Institute members: file servers for Macintosh and NetWare users, some print servers that accept printing requests from PC and UNIX users, a computational server that provides sequence analyses and database retrievals, communication servers to the Internet, and so on. The laboratory also provides an information dispatching service to the Internet using the World Wide Web (URL is http://www.nibb.ac.jp).

4. Plant Culture Laboratory

There are a large number of culture boxes, and a limited number of rooms with environmental control for plant culture. In some of these facilities and rooms, experiments can be carried out at the P1 physical containment level.

5. Experimental Farm

This laboratory consists of two 20 m2 glass-houses with precise temperature and humidity control, a small farm, two greenhouses (45 and 88 m2 ) with automatic sprinklers, two open aquariums (30 and 50 t) and several smaller tanks. The laboratory also includes a building with office, storage and work-space.

6. Plant Cell Laboratory

Autotrophic and heterotrophic culture devices and are equipped for experimental cultures of plant and microbial cells. A facility for preparation of plant cell cultures including an aseptic room with clean-benches, is also provided.

7. Laboratory of Stress-Resistant Plants

This laboratory was founded to study transgenic plants with respect to tolerance toward various environmental stresses. It is located in the Agricultural Experimental Station of Nagoya University (30 km from the National Institute for Basic Biology). The laboratory provides a variety of growth chambers that precisely control the conditions of plant growth and facilities for molecular biological, and physiological evaluations of transgenic plants. The laboratory is also a base of domestic and international collaborations devoted to the topic of stress-resistant transgenic plants.

II. Research activities

1. Faculty

The faculty of the Research Support Facility conducts its own research as well as dcientific and administrative public services.

(1) Photobiology: Photoreceptive and signal trans-duction mechanisms of phototaxis of single-celled, flagellate algae are studied action spectroscopically (Watanabe 1995, In CRC Handbook of Organic Photochemistry and Photobiology) by measuring computerized-videomiceographs of the motile behavior of the cells at the cellular and subcellular levels (Erata et al. 1995, Protoplasma). Photo-receptive and signal tranduction mechanisms of algal gametogenesis are also studied by action spectroscopy.

(2) Developmental Biology: Notch is an integral cell surface membrane protein that is known to play a key role in developmental cell-cell interactions in Drosophila, particularly in lateral specification of neural versus epidermal cell fates, a process described thus far only in invertebrates. It is thought to act by a direct signaling pathway rather than through one of the classical signal transduction cascades. The mammalian genome is known to contain three Notch homologues but their developmental significance is not clear. To investigate their role in mammalian development, we have sequenced the murine Notch 2 cDNA, determined the primary sequence of its protein, and have investigated its genomic organization. We are now attempting to produce a mutant in which the ankyrin repeat region of Notch 2 is replaced by lacZ. Analysis of the mutant phenotype will provide us with insights about the significance of the repeat in Notch 2 signal transduction in relation to its developmental importance.

(3) Computational Biology: Efforts to develop new methodology for sequence analysis have been continued. A system to predict protein localization sites from the sequences had been developed and is now open to the public through the Internet (http://psort.nibb.ac.jp). Sequence motifs are thought to be good indices of biological functions. Methodology of protein sequence analysis based on sequence motifs has been studied and is implemented as a computer program. The product of computer assistance for sequence analysis is being constructed using the World Wide Web.
Many kind of databases become available in recent years, but almost all of them are those of molecular information such as nucleic acids or amino acids sequences. It is also desired to construct a database for biological functions like networks of the regulation of gene expression. As a model case, Bacillus subtilis genome database is constructed to represent the categorized classification of gene products in collaboration with Dr. N. Ogasawara (NAIST) and Human Genome Center, University of Tokyo. Other kind of biological functional databases including image data are planned to represent the accumulated knowledge of development, differ-entiation, and morphogenesis.

2. Cooperative Research Program for the Okazaki Large Spectrograph

The NIBB Cooperative Research Program for the Use of the OLS supports about 30 projects every year conducted by visiting scientists including foreign scientists as well as those in the Institute.
Action spectroscopical studies for various regulatory and damaging actions of light on living organisms, biological molecules, and organic molecules have been conducted (Watanabe, 1995, In CRC Handbook of Organic Photochemistry and Photobiology).

Publication List:

I. Faculty

Erata, M., Kubota, M., Takahashi, T., Inouye, I. and Watanabe, M. (1995) Ultrastructure and phototactic action spectra of two genera of cryptophyte flagellate algae, Cryptomonas and Chroomonas. Protoplasma, 188, 258-266.

Higuchi, M., Kiyama, H., Hayakawa, T., Hamada, Y. and Tsujimoto, Y. (1995) Differential expression of Notch1 and Notch 2 in developing and adult mouse brain, Mol. Brain Research, 29, 263-272.

Nakamura, S., Kawanishi, E., Nakamura, S., Watanabe, M., and Kojima, M. K. (1995) A new paralyzed flagella mutant, OC-10, in Chlamydomonas reinhardtii that can be reactivated with ATP. Phycol. Res., 43, 65-69.

Watanabe, M. (1995) Action spectroscopy : photomovement and photomorphogenesis spectra. In "CRC Handbook of Organic Photochemistry and Photobiology", (Edited by B. Horspool and P.-S. Song), CRC Press, Boca Raton, pp. 1276-1288.

II. Cooperative Research Program for the Okazaki Large Spectrograph

Erata, M., Kubota, M., Takahashi, T., Inouye, I. and Watanabe, M. (1995) Ultrastructure and phototactic action spectra of two genera of cryptophyte flagellate algae, Cryptomonas and Chroomonas. Protoplasma, 188, 258-266.

Iseki, M. and Wada, S. (1995) Action spectrum in ultraviolet region for phototropism of Bryosis rhizoids. Plant Cell Physiol. 36, 1033-1040.

Miyoshi, N., Kondo, T., Kubota, M., Ishiguro, K., Watanabe, M. and Fukuda, M. (1995) Effect of molecular formation of photosensitization for generation of active oxygen species. Photomed. Photobiol. 16, 79-82.

Nakamura, S., Kawanishi, E., Nakamura, S., Watanabe, M., and Kojima, M. K. (1995) A new paralyzed flagella mutant, OC-10, in Chlamydomonas reinhardtii that can be reactivated with ATP. Phycol. Res., 43, 65-69,

Takano, J.-I., Koizumi, H., Ohkawara, A., Kamo, N. and Ueda, T. (1995). Ultraviolet action spectra for peroxide generation in human and pig epidermail keratinocytes loaded with dihydrorhodamine 123. Arch Dermatol. Res. 287, 321-325.

Torikai, A., Chigita, K., Okisaki, F. and Nagata, M. (1995). Photo-oxidative degradation of polyethylene containing flame-retardant agents by monochromatic light. J. Appl. Polym. Sci. 58, 685-690.

Torikai, A., Hattori, A. and Eguchi, T. (1995). Wavelength effect on the photoinduced reaction of polymethylmethacrylate. J. Polymer Sci. :Part A: Polymer Chem. 33, 1867-1871.

Torikai, A., Kobatake, T., Okisaki, F. and Shuyama, H. (1995) Photodegradation of polystyrene containing flame-retardants: wavelength sensitivity and efficiency of degradation. Polymer Degradn. Stab. 50, 261-267.

Torikai, A. and Mitsuoka, T. (1995) Electron spin resonance studies of poly(methyl methacrylate) irradiated with monochromatie light. J. Appl. Polym. Sci. 55, 1703-1706.

Ueda, T. (1995). Spatiotemporal dynamics of glycolysis and cellular metabolism: toward intelligence by nonlinear chemical processes. Sensors Materials 7, 147-157.

Watanabe,M. (1995). Action spectroscopy : photomovement and photomorphogenesis spectra. In "CRC Handbook of Organic Photochemistry and Photobiology", (Edited by B. Horspool and P.-S. Song), CRC Press, Boca Raton, pp. 1276-1288.


CONTENTS


RADIOISOTOPE FACILITY
(Managed by NIBB)


Head: Takashi Horiuchi
Associate Professor: Kazuo Ogawa
NIBB Postdoctoral Fellow: Hiroyuki Takai
Technical Staffs: Kazuhiko Furukawa (Radiation Protection Supervisor), Yosuke Kato (Radiation Protection Supervisor), Yoshimi Matsuda (Radiation Protection Supervisor)

This Facility consists of a main center where a variety of radioisotopes such as 22Na, 125I, 32P, 3H and 14C are handled as well as various species of Gamma-ray emitting nuclides and two subcenters, one placed in the NIBB and the other in the NIPS. At the subcenters, only a limited variety of radioisotopes such as 35S and 32P are processed. The members of the Radioisotope Facility are engaged in maintaining and controlling both the center and subcenters, and provide users an appropriate guidance for radioisotope handling.
In 1995, the new system for the going in and out the controlled area was introduced. ID card has been issued to each registered individual and non-registered persons are allowed to enter the controlled area. In this system, when he or she goes in and out the controlled area, his or her names, times, and places are automatically recorded by a computer. Furthermore, the renewal of the radiation monitoring system and the radioactive contamination assessment system in this Facility has been supported by the secondary supplementary budget of the Ministry of Education, Science and Culture and is going on until the end of Mach, 1996. In these refreshed systems, the radioactivities of air, and draining in the controlled area of the three places will be monitored by a computer for 24 hours. The third subcenter of this Facility will open in the next spring (1997) in the building of the Laboratory of Gene Expression and Regulation that is now under construction.
The teaching staffs are also engaged in their own research on the structure and function of dynein motor protein. Dyneins are a group of microtubule-activated ATPases that serve to convert chemical energy into mechanical energy. They have been divided into two large subgroups, namely, the axonemal and cytoplasmic dyneins. Figure 1 shows the localization of two dyneins in the outer arms (Ogawa et al., 1977) and the mitotic apparatus (Mohri et al., 1976) that have been visualized by the same antibodies directed against the motor domain of axonemal dynein (fragment A).
The native dyneins are very large. They range in molecular mass up to 1 to 2x106 daltons and they are complex proteins. Each dynein contains two or three heavy chains (HCs) with ATPase activity, which range in molecular mass up to 500 kDa. The motor activity of dynein is associated with these chains. Some functional differences have been reported between HCs of outer-arm dynein. Sea urchin outer-arm dynein is a heterodimer of HCs (Alpha and Beta) and at least the Beta-HC is able to induce gliding of microtubules in vitro. The Alpha-HC might amplify the function of Beta-HC and it has been reported to have no motile activity. After the first cloning of Beta-HC from sea urchin ciliary axonemes (Gibbons et al., 1991; Ogawa, 1991), the sequences of HCs of axonemal and cytoplasmic dyneins from a variety of organisms were determined in their entirety. Without exception, all the HCs cloned to date contain four P-loop (ATP-binding) sequences in the midregion of the molecule. Thus, they can be classified as a four P-loop family.
The outer-arm dyneins contain two or three proteins that range in molecular mass from 70 to 120 kDa and copurify with HCs. ICs of sea urchin outer-arm dynein are abbreviated as IC1, IC2, and IC3. Those of Chlamydomonas are called IC78 and IC69, and ICs of cytoplasmic dynein are called IC74. Chlamydomonas IC78 and IC69 were cloned by Wilkerson et al. (1995) and Mitchell and Kang (1991),respectively. The sequences of sea urchin IC2 and IC3 were determined by Ogawa et al. (1995).


Fig. 1. Localization of dynein in sea urchin sperm axoneme (A) and a cleaving egg (B).


Fig .2. Relative positions of WD repeats (filled boxes) in sea urchin outer-arm dynein IC2 and IC3, Chlamydomonas outer-arm dynein IC78 and IC69, and rat cytoplasmic dynein IC74. Colours mean subclass of ICs.

IC1 has recently been cloned (Ogawa, accession number D63884). Rat brain IC74 was cloned by Paschal et al. (1992). Thus, all the ICs found in the axonemal and cytoplasmic dyneins of the model organisms used for studies of dynein function have been completely sequenced. Comparison of amino acid sequences of IC2 and IC3 with those of IC78 and IC69 and with that of IC74 showed that, although all five ICs are homologous, IC2 is much more closely related to IC78, and IC3 is much more closely related to IC69, than either sea urchin chain or either Chlamydomonas chain is related to each other. Regions of similarity between all five ICs are limited to the carboxy-terminal halves of the molecules. Similarity are due primarily to conservation of the WD repeats in all of these chains. The WD repeats are involved in protein-protein interactions in a large family of regulatory molecules (Neer et al., 1994). The relative positions of WD repeats in these chains are shown schematically in Fig. 2.
A parsimony tree for these chains (Ogawa et al., 1995) shows that, although the carboxy-terminal halves of all of these chains contain WD repeats, the chains can be divided into three distinct subclasses (IC3 plus IC69, IC2 plus IC78, and IC78). By contrast, sea urchin IC1 is not a member of the WD family. Sequence analysis showed that IC1 consists of a thioredoxin-like (TRXL) sequence and three nucleoside diphosphate kinase-like (NDKL) sequences. IC1 might play a dynamic role in flagellar bending and/or wave propagation.

Publication List:

Ogawa, K., Kamiya, R., Wilkerson, C. G. and Witman, G. B. (1995) Interspecies conservation of outer arm dynein intermediate chain sequences defines two intermediate chain subclasses. Mol. Biol. Cell 6, 685-696.

Shimizu, H., Majima, T., Takai, H., Inaba, K. and Tomie, T. (1995) Morphological changes of wrasse sperm axoneme after their motility initiation observed with use of Atomic Force Microscopy. SPIE 2384, 45-51.

Takai, H. and Morisawa, M. (1995) Change in intracellular K concentration caused by external osmolarity change regulates sperm motility of marine and freshwater teleosts. J. Cell Sci. 108, 1175-1181.


CONTENTS


CENTER FOR ANALYTICAL INSTRUMENTS
(managed by NIBB)


Head of Center: Masaharu Noda
Technical Staffs: Akio Murakami, Yukiko Kabeya, Yumiko Makino, Sonoko Ohsawa, Takeshi Mizutani

The center provides analytical instruments for biological and biophysical studies. These instruments consist of the following four groups and are supported by experienced technical staffs. Each group is equipped with instruments for general use as listed below.

Instruments for Protein and Gene Analysis

Amino Acid Analyzer
HITACHI 835
Automatic Plasmid Isolation System
KURABO PI-100
DNA Sequencers
ABI 370A, 373A-36
DNA/RNA Synthesizers
ABI 381A, 392
Nucleic Acid Extractor
ABI 340A
Peptide Synthesizers
ABI 430A, 431A, 432A
Protein Sequencers
ABI 470A, 473A, 492

Instruments for Chemical Analysis

Capillary Electrophoresis
ABI 270A
Gas Chromatographs
SHIMADZU GC-7APTF, GC-14APFSC
Glycoprotein Analysis System
TAKARA Glyco-Tag
High Performance Liquid Chromatographs
SHIMADZU LC-10AD, 6AD
Preparative Electrophoresis System
ABI 230A
Preparative Ultracentrifuges
BECKMAN L8-80, L5-75
Table-top Ultracentrifuges
BECKMAN TL-100
Micro Preparative System
PHARMACIA SMART System

Instruments for Physical and Spectroscopic Analysis

Atomic Absorption Spectrophotometer
PERKIN-ELMER 603
Dual Wavelength Spectrophotometer
HITACHI 557
EPR Spectrometer
BRUKER ER-200D
GC/Mass Spectrometer
JEOL DX-300
Inductively Coupled Plasma Spectrometer
SEIKO SPS 1200A
Infrared Spectrophotometer
JASCO A-302
Laser Raman Spectrophotometer
JASCO R-800
Light Scattering Photometer
CHROMATIX KMX-6DC
NMR Spectrometer
BRUKER AMX-360wb
Spectrofluorometers
HITACHI 850
SIMADZU RF-5000
Spectrophotometers
HITACHI 330
PERKIN ELMER Lambda Bio
Spectropolarimeter
JASCO J-40S
DELFIA Research Fluorometer
PHARMACIA

Instruments for Microscopic and Image Analysis

Bio Imaging Analyzers

FUJIFILM BAS 2000
Imaging Analysing Systems
KONTRON IBAS-I & II
Electrophoresis Imaging System
PDI The Discovery Series
Microscopes
CARL ZEISS Axiophot, Axiovert
Microscope Photometer
CARL ZEISS MPM 03-FL
Microdensitometer
JOYCE LOEBL 3CS


CONTENTS