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APRIL !"#$ RIKEN RESEARCH VOLUME % NUMBER & Melting point 900 MHz NMR facility in Yokohama © 2013 RIKEN TABLE OF CONTENTS Table of contents HIGHLIGHT OF THE MONTH 4 A vertebrate family reunion RESEARCH HIGHLIGHTS 6 Melting back and forth 7 Silicon’s double magic # 8 Watching bioactive molecules at work 9 Cancer drugs taking shape 10 Stopping the rot 11 Understanding metabolism through computer predictions 12 Cellular networks up close 13 Stem cell therapy for Parkinson’s disease $ FRONTLINE 14 Generating cancer blueprints for future therapies RIKEN PEOPLE 18 Masayo Takahashi, Laboratory for Retinal Regeneration !# !" RIKEN RESEARCH RIKEN, Japan’s flagship research institute, makers interested in science and aims to raise conducts basic and applied experimental global awareness of RIKEN and its research. research in a wide range of science and Sendai technology fields including physics, For further information on the research chemistry, medical science, biology and presented in this publication or to arrange an Wako engineering. Initially established as a private interview with a researcher, please contact: Nagoya research foundation in Tokyo in !"!#, RIKEN Tsukuba became an independent administrative RIKEN Global Relations Office Tokyo Yokohama institution in $%%&. $'!, Hirosawa, Wako, Saitama, &(!'%!"), Japan Osaka TEL: +)! *) *+$ !$$( Kobe RIKEN RESEARCH is a website and print FAX: +)! *) *+& &+)# Harima publication intended to highlight the best E'Mail: [email protected] research being published by RIKEN. It is written URL: www.riken research.riken.jp for a broad scientific audience and policy www.riken.jp RIKEN supports research at nine sites across Japan RIKEN RESEARCH | VOL. ! | NUMBER " | APRIL #$%& | www.rikenresearch.riken.jp 3 HIGHLIGHT OF THE MONTH Biology A vertebrate family reunion By demonstrating the close ‘relatedness’ of two primitive jawless fish, scientists begin to assemble a more accurate depiction of the early history of vertebrate evolution Roughly !"" million years ago, our ances# tors began developing a physical charac# teristic that is almost universal among modern vertebrates: jaws. In fact, the hagfish and the lamprey are the only known living vertebrates that do not belong to this ‘gnathostome’ majority. These jawless ‘cyclostomes’ are instead generally considered to be holdovers from the earliest days of the vertebrate lineage. Yet hagfishes and lampreys bear striking physiological differences, calling into question the closeness of their relat# edness and their relative positions on the ‘evolutionary tree’. New research from Shigeru Kuratani’s team at the RIKEN Center for Developmental Biology Figure 1: Adult hagfish, Eptatretus burgeri, seen from dorsal view. now provides striking evidence that © !"#$ Shigeru Kuratani, RIKEN Center for Developmental Biology these two fish should indeed be grouped together, based on a shared process of Back to the beginning craniofacial development that is distinct to collect enough adult hagfishes to allow $ from gnathostomes . One major developmental difference tissue to be cultivated in the laboratory, %e hagfish &Fig. $' lacks several features observed in hagfishes pertains to an providing unprecedented access to that define the vertebrate body plan, with essential endocrine gland known as freshly laid hagfish eggs &Fig. )'. This a head that looks strikingly different from the adenohypophysis. In lampreys and achievement has given the team valuable the lamprey in cross#section, leading some other vertebrates, this organ develops insights into the embryology of this scientists to posit that hagfishes repre# from an embryonic tissue called the enigmatic species. sent a more primitive digression from ectoderm, while previous analyses have %rough close examination of crani# the vertebrate lineage. %is would mean suggested that the hagfish adenohy# ofacial formation at precise timepoints lampreys are a separate, more direct ante# pophysis arises from an entirely differ# in hagfish development with the aim cedent of gnathostomes, undermining the ent embryonic tissue(the endoderm. of identifying similarities and differ# idea that both species belong to a single However, Kuratani was concerned about ences relative to the lamprey and a rep# offshoot group of cyclostomes. the foundations of that conclusion. resentative gnathostome species, the “It is a recent trend to view each “%ose observations were partly based on cloudy catshark, Kuratani’s team has animal lineage's developmental program ill#fixed samples with lots of tissue dis# made a number of important observa# as diverging and differing from each tortion, and from very few specimens,” tions. For example, during an embry# other,” says Kuratani, “and not viewing he says. onic stage known as the neurula, the one specific program as ancestral to the Historically, hagfish eggs have proved endoderm and ectoderm are brought others.” To resolve this debate, Kuratani remarkably difficult to obtain. By into direct proximity with one another and colleagues began a deep analysis of working with local Japanese fishermen, at a structure known as the oropharyn# hagfish development. however, Kuratani’s team has been able geal membrane, which ultimately forms 4 RIKEN RESEARCH | VOL. ! | NUMBER " | APRIL #$%& | www.rikenresearch.riken.jp HIGHLIGHT OF THE MONTH the mouth. However, the research# tree. “With these findings, people will development, but they also intend to ers identified another membrane in be convinced that these animals are evo# broaden their investigation of early evo# the hagfish neurula that appears to be lutionarily very close to each other,” says lutionary history to include the amphi# unique to this group of species, which Kuratani, “and it also helps us identify oxus(also known as a lancelet(which they termed the secondary oropharyn# homologous organs and structures in is an invertebrate that scientists see as a geal membrane &SOM'. %ey concluded adult animals, which is very hard with close precursor to the emergence of ver# that previous investigators used the simple dissection.” tebrate species. “We hope to reconstruct wrong ‘landmark’, mistaking the SOM Their results also offer some other early vertebrate evolution and the estab# for the oropharyngeal membrane, and interesting insights. For example, the lishment of the vertebrate body plan by thereby incorrectly positioned the origin physiological oddities that have helped describing it as changes in the develop# of the adenohypophysis within the confound the positioning of hagfishes on mental program associated with specific endoderm. Further embryonic analysis the evolutionary timeline(such as the genomic changes,” says Kuratani. confirmed that this gland originates in absence of a vertebral column(suggest !. Oisi, Y., Ota, K.G., Kuraku, S., Fujimoto, S. & the hagfish ectoderm, as with the shark that this species may have actually shed Kuratani, S. Craniofacial development of hag" and lamprey. certain ‘advanced’ features found in fishes and the evolution of vertebrates. Nature Kuratani and his colleagues identified lampreys to accommodate its distinc# !"#, !#$%!&$ '($!)*. other, clear similarities in lamprey and tive lifestyle. “Hagfishes dive into rotten hagfish craniofacial development. In bodies of whales and large fish,” explains ABOUT THE RESEARCHER both animals the nostril and adenohy# Kuratani, “and make a movable knot in pophysis originate from a single source their long body to pull themselves out of tissue, remaining adjacent in the mature the body they were eating.” By compari# animal. In comparison, these structures son, lampreys feed on small organisms arise from two separate tissues in gna# in the water or by attaching parasitically thostome species, and mature gnathos# to the exterior of other fish. tomes typically have two nostrils &rather Most importantly, this embryologi# than the one observed in cyclostomes' cal comparative analysis has identi# positioned further apart from the adeno# fied potential commonalities between hypophysis, which is in turn connected processes observed in cyclostome devel# with the mouth and throat. opment and those seen in the most primitive gnathostomes, indicating the Uncovering an ancestral possibility of a shared ‘basic blueprint’ for connection head formation. “%is suggests a pattern © !"#$ RIKEN These and other findings from Kura# that could be regarded as ancestral for Shigeru Kuratani received his PhD from tani’s team strongly support a model in all vertebrates,” concludes Kuratani. the Kyoto University Department of which hagfishes and lampreys belong to In future work, his team will continue Zoology. From 1988 to 1991 he worked a common ‘branch’ of the evolutionary to explore the mysteries of hagfish in experimental embryology in the Department of Anatomy at the Medical College of Georgia before moving to the Biochemistry Department at the Baylor College of Medicine, where he was engaged in molecular embryological research. He returned to Japan in 1994 to take on the position of associate professor at the Institute of Medical Embryology and Genetics at the Kumamoto University School of Medicine. He moved to Okayama University to assume a professorship in the Department of Biology in 1997, where he remained until he was appointed Shigeru Kuratani, RIKEN Center for Developmental Biology Developmental for RIKEN Center Shigeru Kuratani, team leader at the RIKEN Center for !"#$ Developmental Biology. He was appointed © group director in 2005. Kuratani’s research focuses on vertebrate head