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Laboratory for Immunogenomics Group director Osamu Ohara Senior Research Scientist: Hiroshi Kitamura Research Scientist Research Associate Technical Staff Temporary employee : Yayoi Kimura : Atsushi Hijikata : Ryo Yokoyama, Tomoko Yuasa, Masatoshi Ito, Miho Izawa, Chisato Kikuguchi : Yuki Kobayashi, Tetsuhiro Moriya, Masako Mori, Seiko Watanabe, Nobutake Suzuki, Satomi Takahashi, Kayoko Nagata, Aoi Ozawa, Noriko Sawai, Tatsufumi Nagase, Yukiko Sakaguchi An important and basic mission of our research group is to function as a “Gateway” to genomics for immunologists. To achieve this goal, our research group has taken a threepronged approach: (1) central support activities; (2) strategic and collaborative research activities; and (3) exploratory research activities aimed at new technology development. In 2007, we have made a significant effort to enhance strategic and collaborative research activities, particularly for the human primary immunodeficiency (PID) network project. We have also strengthened our collaborative relationships with other research groups at RCAI even more than before. For example, our collaboration with the Research Unit for Human Disease Model (unit leader, Dr. Ishikawa) has given us many opportunities to learn how to make genomic approaches more fruitful in immunology. One of our current interests that originated from this collaboration is how to analyze mRNA and protein profiles of very limited numbers of immune cells. This pursuit was originally motivated by the need to solve practical problems frequently encountered in the central support activities as well as in collaborative research activities. However, if we can make a breakthrough in genomic analysis at the single cell level, we believe that this path will lead us to substantial breakthroughs in analysis of complicated immune systems from a systems biology viewpoint. We anticipate that the interactions among our three-pronged research activities, which are driven by collaboration with immunologists, will play a crucial role in development of Immunogenomics at RCAI. Below we describe two of our research activities in 2007. Enhancement of an open-access Immunogenomics database, RefDIC As explained in the 2006 annual report, we launched an open-access Immunogenomics reference database of immune cells, abbreviated as RefDIC, and have described this database in a recent publication (Bioinformatics 2007). However, it was obvious from the outset that the dataset in RefDIC had to keep growing in size as well as in quality. To achieve this, we have taken advantage of our central support activities for DNA chip-based mRNA profiling: Because we analyzed all the samples for mRNA profiling in the same way as those for the dataset of RefDIC, it was quite straightforward to incorporate the data from either the central Assistant : Kazuyo Nomura 80
Recent publications Figure 1 Enhanced mRNA profile viewer in RefDIC support activities or the strategic/collaborative research activities after obtaining approval from clients/collaborators for deposition of the data into RefDIC. We are confident that this approach will allow for sustainable growth of RefDIC. In fact, the number of the microarray datasets was only 159 when RefDIC was opened to the public last year, but now the total number of datasets currently accumulated exceeds 1200 at the end of 2007 (Figure1 upper panel). We also had to revise the informational platform of RefDIC to accommodate the increased number of the datasets. Figure 1 shows an updated version of the RefDIC mRNA profile viewer as an example. RefDIC has been accessed by a large number of immunologists world-wide and will keep growing as well as becoming a more integrated Immunogenomics database through links to other bioinformatics databases and incorporation of new primary data from our own experiments. The Primary Immunodeficiency Disease Project The aim of this project is to analyze the immunological features and genetic causes of primary immunodeficiency diseases (PID) in a collaborative framework with clinical immunologists and was initiated in late 2006. Towards this end, various platforms are needed. The first is an informational platform to fill the gaps among patients, clinicians, basic immunologists, and genomic scientists. The second is a platform for analysis of PID samples from immunological and genetic perspectives. The third is an integrated database which stores various threads of information regarding PID and will enable us to make a diagnosis more accurately and rapidly than before. The informational and genomic technology will certainly play a crucial role in construction of such multidisciplinary platforms. In practice, we set up a collaboration framework with clinical immunologists in 13 Japanese universities/colleges, the Kazusa DNA Research Institute (KDRI;Chiba, Japan), and the Institute of Bioinformatics (IOB;Bangalore, India) for this project. In this regard, the PID project might be viewed as a pioneering venture for RCAI in an immune disease-oriented multidisciplinary collaboration. In RCAI, the Immunological Memory Research Group, the Immunogenomics Research Group, the Research Unit for Human Disease Model and the Immunoinformatics Research Unit are all involved in this project (See Collaborative Networks). Our research group (including the RCAI IT-support group) has worked particularly for construction of the clinical information repository of PID patients and for construction of the DNA diagnosis framework in collaboration with clinical immunologists and KDRI. Construction of the open-access PID database is also being conducted by our group, in collaboration with the Immunoinformatics Research Unit, KDRI and IOB. Consequently, the clinical information repository, designated PIDJ, is now open to the public and more than 40 patient samples were subjected to DNA analytical diagnosis in 2007. We will make every effort to mature these platforms to support patients and clinicians who are fighting PID. Figure 2 The framework of the primary immunodeficiency disease project Kitamura H, Ito M, Yuasa T, Kikuguchi C, Hijikata A, Takayama M, Kimura Y, Yokoyama R, Kaji T, Ohara O. Genome-wide identification and characterization of transcripts translationally regulated by bacterial lipopolysaccharide in macrophagelike J774.1 cells. Physiol Genomics 33, 121-132 (2008) Wakiyama M, Takimoto K, Ohara O, Yokoyama S. Let-7 microRNAmediated mRNA deadenylation and translational repression in a mammalian cell-free system. Genes Dev. 21, 1857-1862 (2007) Hijikata A, Kitamura H, Kimura Y, Yokoyama R, Hori S, Ishii Y., Kanagawa O, Kawamoto H, Koseki H, Kubo M, Kurosaki T, Ohno H, O-Wang J, Saito H, Saito T, Sato K, Tanaka M, Taniguchi M, Taniuchi I, Watanabe T, Aiba Y, Bao Y, Hase K, Kikuchi K, Nakata M, Oboki K, Okamoto M, Sakuma M, Sato K, Seino K-I, Setoguchi R, Suematsu S, Watarai H, Yamasaki S, Ohara O. Construction of an open-access database that integrates crossreference information from the transcriptome and proteome of immune cells. Bioinformatics 23, 2934-2941 (2007) Ishikawa F, Yoshida S, Saito Y, Hijikata A, Kitamura H, Tanaka S, Nakamura R, Tanaka T, Tomiyama H, Saito N, Fukata M, Miyamoto T, Lyons B, Ohshima K, Ucida N, Taniguchi S, Ohara O, Akashi K, Harada M, Shultz DL Chemotherapy-resistant human AML stem cells home to and engraft within the bone marrow endosteal region. Nature Biotechnology 25, 1315-1321 (2007) Matsubara K, Imai K, Okada S, Miki M, Ishikawa N, Tsumura M, Kato T, Ohara O, Nonoyama S, Kobayashi M. Severe developmental delay and epilepsy in a Japanese patient with severe congenital neutropenia due to HAX1 deficiency. Haematologica 92, e123-125 (2007) 81
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Special Advisor Kimishige Ishizaka
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i v Organization Director’s Repor
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Director’s Report This is the fou
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RCAI research retreat program. Prev
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Haruhiko Koseki Good housekeeping A
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Hiroshi Ohno Cell fusion may create
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Tsuneyasu Kaisho Halting the inflam
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Takashi Saito Signaling simplified
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Makio Tokunaga Looking beneath the
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Tomohiro Kurosaki Immune cells stim
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Ichiro Taniuchi How cells switch fr
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Shin-ichiro Fujii On the road to a
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Award Winners 2007 Shohei Hori and
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found a factor called PDLIM2 that l
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2007 Excellent Paper Award and Exce
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Laboratory for Developmental Geneti
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Research Unit for Lymphocyte Clonin
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Laboratory for Lymphocyte Developme
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