Research Subjects

How Genetic Information Is Inherited?
Genetic information that consists of nucleotide sequences of DNA is essential for living organisms and is inherited from cells to cells, organisms to organisms. To maintain genetic information chromosome DNA is correctly duplicated and transmitted during a cell division cycle. The process of chromosome DNA replication is regulated to ensure faithful duplication of the entire genome only once in a cell cycle. When DNA is damaged by ultraviolet light, X-ray or nucleotide modification, it has to be repaired before transmitted into daughter cells. Failure in correct inheritance of DNA may cause cell death or cancer in some case. On the other hand, genetic information is mixed by recombination to generate diversity of the genome, so that the life can evolve a new species. We are studying the fundamental mechanisms of DNA replication, repair and recombination at a molecular level. We use a model organism, fission yeast (Schizosaccharomyces pombe) that is a unicellular eukaryote suitable for the fundamental studies.

Two-dimensional gel electrophoresis of replication intermediates at replication origin ars2004 on chromosome II in haploid fission yeast cells arrested in early S phase (A). DNA microarray results showing locations of newly synthesized DNA (green) and initiator protein Orc1 (brown) at the ars2004 locus (B).

Masukata Lab

How Cells Proliferate?
All living things are made of cells. Proliferating cells faithfully duplicate their genetic information and transmit the duplicated information to daughter cells. Cells also differentiate into special cells so that they form tissues or organs. Normal cells are unable to proliferate infinitely, but divides definite times to be senescent cells. Cells commit even suicide, which is called apoptosis, and it plays a crucial role in removing unnecessary cells from multi-cellular organisms. Previous studies have established that various features found in proliferating cells, in particular the mechanisms for cell division are conserved from unicellular yeast to multi-cellular human. Evolution of life from a single cell originated about three hundred million years ago, may explain the unity of cells, but the evolution also creates astonishingly different organisms on our earth. Our research goal is to understand molecular machineries involved in duplication and transmission of eukaryotic chromosome, using Xenopus eggs and human cells. Eventually, we would like to know where we are from.

Proliferating HeLa cells at various cell cycle stages.

Takisawa Lab

Intracellular Homeostasis of Ions
As you use a metaphor "you should not send salt to your enemy", salt (NaCl) is essential for living organisms. In blood, Na+ is maintained as high as in sea water, while intracellular Na+ is very low. Therefore, there is a concentration gradient of Na+ established across cytoplasmic membranes. By this concentration gradient Na+ can move into cells through membrane integrated proteins providing a pore for Na+. This Na+ movement sometimes drives flow of other ions and solutes like glucose or amino acids, and also induces special membrane devices like flagella. We are interested in the membrane proteins providing a pore for Na+. Questions are raised how the Na+ pore is made, how Na+ movement drives other ion or solute flow. The regulation of this Na+ flow across the membrane is required for intracellular pH regulation as well, because a major counter ion driven by Na+ flow is H+. We are studying molecular architecture of Na+/H+ antiporter, a major Na+ transporting protein found in bacteria to human, by molecular and biochemical approaches. Malfunction of this Na+/H+ antiporter leads to illness like cancer, epilepsy and so on, suggesting that our study is also useful for medical sciences.

Fig.1: Images of the membrane proteins and a transporter, Fig.2: Dimer formation and ion antiport in Na+/H+ antiporter.

Kanazawa Lab

Structures of Proteins
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Fukuyama Lab

Protein Designing
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Kuramitsu Lab

Sensory Biology
Our senses are the tools to know the world outside of each individual. Our sensory organs can sense the stimuli like photons for vision, chemical substances for taste and smell, mechanical pressure for touch and auditory, etc. The aim of the study in this lab is to find out the detection mechanisms of these stimuli at the molecular and the cellular level.

Our current focus is directed to the detection mechanisms of photons in cone photoreceptors. In our retina, there are two kinds of photoreceptors, rods and cones. Our way of seeing is determined by the nature of these photoreceptors. Light-sensitivity is very high in rods but it is low in cones. For this reason, rods mediate twilight vision and cones mediate daylight vision. Time resolution is much better in cones and there are three kinds of cones, each of which is sensitive to blue, green or red. For these reasons, we see the outside world with cones in daylight with good time resolution with color. In twilight, we cannot detect color, and it is hard to see an object moving fast. We are currently interested in the molecular mechanisms of these differences between rods and cones.

Our lab is the first that succeeded in obtaining purified rods in a quantity large enough to do biochemical study. Using purified rods and cones, we are comparing the reactions in rods and cones to find out which reaction(s) is responsible for determining the nature of these cells. We mainly use biochemical approaches. However, the results obtained in those studies must be tested at a cellular level and we utilize electrophysiological techniques for this purpose when necessary.

Purified rods (left) and cones (middle) and photocurrent measurement with suction electrode (right).

Kawamura Lab

Mechanism of Memory
The brain is a mass of an astronomical number of nerve cells. Memory is established through the changes in the network formed by those cells after experiencing an event. To know what changes are critical and how those changes occur, we are examining simplified neural circuits reproduced in a petri dish, since the most fundamental mechanism(s) should be preserved even in such circumstances. For example, the level of calcium ion rises rapidly upon neural activity to lead to an activation of calcium-dependent chain reaction of enzymes, all the same as in the cells in animal.

When a molecule called ‘NMDA receptor’ is activated, the nerve cell’s calcium level rises rapidly at the place where the molecule exists (low calcium is shown in blue, high in red).

Ogura Lab

Muscle -How Does It Move?
Contraction is triggered by calcium from sarcoplasmic reticulum in a muscle cell. Its relaxation is induced by calcium uptake into the reticulum. How is such a specially designed muscle cell developed and differentiated? We are studying this mechanism and searching for factors as molecules. On the other hand, key proteins are myosin and actin. Myosin molecule moves and generates force by ATP hydrolysis on the actin filament. But the mechanism how it moves is not fully understood at molecular and atomic level. How does troponin-tropomyosin on the thin filament regulate muscle contraction and relaxation in the presence and absence of calcium, respectively? How does calcium pump protein uptake calcium into the reticulum? Using a newly developed technique, we are able to measure a size of 1/10,000,000~1/100,000 mm of protein actively working. Recently, we are also studying on how the nerve motor protein kinesin moves on microtubules and photo-receptor rhodopsin works on the retina.

Arata Lab

Research on Plant Growth and Development
We are interested in how signaling molecules regulate plant growth. To this goal, we are investigating biosynthesis and perception mechanisms of cytokinin. Cytokinin is an important plant hormone that regulates cell division and differentiation of plants. We have clarified the biosynthetic pathways of cytokinins, identified the key genes for cytokinin biosynthesis, and identified cytokinin receptors. The figure depicts current understanding of cytokinin signal transduction. To understand the role of cytokinins on plant development, we also modulated cytokinin-related genes by molecular-genetic means, and demonstrated the importance of cytokinins. We are also screening for new cell-to-cell mediators involved in plant development, and identified a number of those that regulate plant development.

Kakimoto Lab

Ecological and Physiological Studies of Plant Functions
When you study functions of biological systems, you may have two types of questions, namely, ‘Why questions’ that ask the reason and significance of their functions, and ‘How questions’ that ask the mechanism responsible for their functions. Basically, ecologists ask ‘Why questions’ while physiologists ask ‘How questions’. However, scientists in both groups have never been always satisfied with their own ways. We are asking ‘How questions’ on the ecological matters and ‘Why questions’ on the physiological matters. Our themes cover various macroscopic to microscopic aspects of plant functions including tree architecture, systemic signal transduction, tropic responses, photosynthetic adaptation, regulation of alternative oxidase, and cytoskeleton. Our experimental procedures consequently encompass ecology, morphology, physiology, cell biology, and even molecular biology.

Left: Chloroplasts face with the intercellular spaces
A: Cross section of the adaxial part of a Spinacia oleracea (spinach) leaf.
B: Paradermal section of the parenchyma cells of Maesa japonica. Arrowhead in A indicates the stoma and the orange circles in B indicate intercellular spaces. Bars: 25 µm.
Right: Respiratory chain of plant mitochondria The alternative oxidase (AOX) is the terminal oxidase and uncoupled from proton transport. In plant mitochondria, uncoupling protein (UCP) can dissipate the proton gradient.

Takagi Lab

Gene Expression

Cells are sensitive to changes in the environments surrounding them and respond by various mechanisms. Control of gene expression is one such mechanism and the control at the transcriptional level is well known. Recently, another mechanism for the control of gene expression has been discovered. Gene expression is controlled at the level of degradation of mRNAs (refer to the right figure). How is mRNA degradation controlled? How is the rate of mRNA degradation controlled? Response to environmental changes involves tactics other than control of gene expression. By moving themselves, cells can escape from unfavorable circumstances such as loss of nutrition. In addition, cells can quickly repair the plasma membranes when damaged by external factors such as force, strong lights, and so on. What mechanisms underlie such abilities of cells? Our research goal is to answer these questions.

Ogihara, Yonesaki Lab

How Eggs Develop into Adult Form?
We all have developed from fertilized eggs 100 µm in diameter. Have you thought about how it can be possible? Our laboratory is working on mechanisms how eggs develop into a well organized adult body using micromanipulative and molecular approaches.

In animal development, embryonic cells not only proliferate, but also generate various types of cells such as epidermis, muscle, neuron, and blood cells. All of these cells are originally derived from a fertilized egg. What kinds of mechanisms are involved in these processes in which some cells are fated to become muscle and other cells to become neuron? Namely, cellular and molecular mechanisms of cell fate determination during embryogenesis are the theme of our laboratory.

We use embryos of ascidian (sea squirt, Halocynthia roretzi) as an experimental material. Ascidian has been regarded as a primitive chordate that evolved to basic vertebrates. Fertilized eggs develop into tadpole larvae within 35 hours of development (Figure). Its embryogenesis has been intensively described in details so that we can predict which cells of the early embryo give rise to which cells of the tadpole larva (Figure, bottom).

Ascidian embryos provide us the unique possibility of understanding various mechanisms of fate determination in every cell type, because the tadpole consists of a small number of cells, and of a few types of tissue. Understanding fate determination mechanisms using this simple model organism with the basic body plan of Chordates would contribute to our knowledge in Developmental Biology.

(Top) 4-cell stage embryos. 3 hours after fertilization. (Middle) Tadpole larvae just before hatching. 35 hours. (Bottom) Fate map of the 110-cell stage blastula and tissue organization of the tadpole. For example red blastomeres give rise to tail muscle cells.

Nishida Lab

Development and Evolution of Animals
Research subjects (keywords): biology of dicyemid mesozoans, origin of multicellular animals, developmental mechanisms of neural crest cells, origin of the vertebrate body plan.

(1) Dicyemid mesozoans are parasites or symbionts living in the kidney of cephalopod mollusks such as cuttlefish and octopus. The dicyemid body consists of only 20 to 30 cells and these are the smallest numbers of cell among multicellular animals. We study various aspects of dicyemid mesozoans, especially their taxonomy, molecular phylogeny, and gene system related to development. Our research subjects also include molecular phylogeny of the host cephalopods, especially cuttlefish.

(2) The neural crest is an embryonic tissue specific to vertebrates and is involved in the development of various vertebrate-specific tissues such as autonomic nervous system and cranial cartilage. We study developmental mechanisms of mouse neural crest cells using techniques of molecular and cell biology. The evolutionary origin of the neural crest is also pursued through the study of development of lampreys which are the most primitive living vertebrates.

(Left) DAPI-stained image of a dicyemid mesozoan. Cell nuclei are brightly stained.
(Right) Migrating neural crest cells. Green fluorescent cells outside the neural tube (NT) represent neural crest cells. Transverse section of the mouse trunk.

Tsuneki Lab