1AGCTMolecular Cell Biology

Cell Biology and Anatomy ——————————————————————————————————————
http://cb.m.u-tokyo.ac.jp/

Cells transport various kinds of proteins, lipids and mRNAs after synthesis to their specific destinations such as several types of membranousorganelles, protein complexes and the mRNA complex. Thus, intracellulartransport is fundamental to cellular functions, survival and morphogenesis. Our laboratory is studying the mechanisms of intracellular transportand cellular morphogenesis, especially focusing on molecular motors,
Kinesin superfamily proteins (KIFs) and microtubule associated proteins(MAPs) using molecular cell biology, biophysics, structural biology, andmolecular genetics.

• Molecular cell biological study of KIFs
• Studies of the mechanism for recognition of and binding to cargoes by KIFs and theregulation of this mechanism• Studies of the mechanisms of differential directional transports and sorting• Studies of the dynamics and mechanism of motility of KIFs using molecular biophysics and structural biology• Molecular genetics of KIFs
• Studies of KIFs and related diseases• Molecular cell biology and molecular genetics of MAPs

Quick freeze-deep etch electron micrographof a mouse nerve axon showing a microtubule (25 nm diameter, linear tube-likestructure) and a cross-bridge linking the
microtubule and a membranous organelle.
Microtubules are a major component of thecytoskeleton and serve as a type of railalong which motor proteins transportorganelles inside cells. (Reproduced fromthe cover of Science vol. 279, Jan 23 1998.)

Structural Biology ————————————————————————————————————————————
http://structure.m.u-tokyo.ac.jp/

Kikkawa lab is interested in flagella/cilia, which works as an actuator aswell as a sensor of cells. We are studying the mechanism of formation andfunction of flagella/cilia using cryo-electron microscopy, opticalmicroscopy, and genetics. We are also developing new technologies toanalyze images taken by microscopes.
Our focuses are:• Molecular formation of flagella and axonemal dyneins.
• Mechanism of force generation by dyneins.
• Structures of microtubule-associated proteins• Development of new image analysis methods for cryo-electron microscopeThree dimensional reconstruction of the outer dynein armmicrotubule complex from wild type. A: rigor state and B:
relaxed state.

14

Cellular Neurobiology —————————————————————————————————————————The Laboratory of Cellular Neurobiology is interested in understanding the molecular mechanisms regulating synapse formationand maintenance, which are essential in proper function of neuralcircuits in the brain. The laboratory is using optical imaging ofsynaptic molecules in live neurons, in combination with molecular biological approaches to modify neuronal functions.

• Molecular architecture of the postsynaptic density• Molecular mechanisms of activity-dependent synapse remodeling• Regulation of synapse functions by glial cells• Regulation of synapse formation and maintenance in vivo

Quantitative fluorescence imaging of cultured hippocampal neurons (green: postsynaptic protein andcalibrated fluorescent microspheres, red: presynaptic
protein, blue: microtubule-associated protein)

Molecular Biology ————————————————————————————————————————————
http://www.cellcycle.m.u-tokyo.ac.jp

We have been studying the molecular mechanism enabling anchorage–independent S phase onsetthat is the key for malignant transformation.

• Understanding the anchorage signal cascades that
control cell cycling• Understanding the mechanism by which anchorage
signals control the G1-S transition

Cellular Signaling —————————————————————————————————————————————
http://biochem2.umin.jp/index_j.html

Our laboratory specializes in biochemistry, molecular and cellularbiology, and genetic engineering to elucidate the roles of lipidmediators in vivo. We further study the molecular mechanism
and biological significance of diversity and asymmetry of cellular
membrane lipids. In collaboration with the Department ofMetabolome, we analyze stimulus induced dynamic changes in
the lipid composition of the cellular membrane.

• Discovery and structural determination of novel lipid mediators• Cloning, functional characterization and K/O studies of enzymes involved in
the metabolism of lipid mediators and receptors for lipid mediators• Structure, function and dynamics of GPCR
• Lipidomics and enzyme characterization of membrance organization
Production of lipid mediators during Lands’ Cycle and activation ofGPCRs(Shimizu,T., Ann. Rev. Pharmacol. Toxicol. 49, 123-150, 2009)15

1

Physiological Chemistry and Metabolism ———————————————————————————
http://bio.m.u-tokyo.ac.jp/

We are investigating signaling mechanisms underlying cell fate determination, morphogenesis andorganogenesis in embryonic development.

• Molecular mechanisms of neural crest fate determination and craniofacial
morphogenesis• Molecular mechanisms of cardiovascular development• Epigenetic control of embryonic development• Roles of microRNA in embryonic development

Transformation of the upper jaw into a lower jaw inendothelin-1 knock-in (misexpressing) mouse (upper).
The lower is the wild-type control.

16