IIIS Laboratory Descriptions

Masashi Yanagisawa / Hiromasa Funato Lab Protein biochemist; cellular signaling specialist

Our laboratory has been conducting a large-scale forward genetic screen of sleep/wake abnormalities in ENU-mutagenized mice. Through this approach, we have very recently identified novel genes that we believe are central players in the fundamental pathway of controlling sleep and wakefulness. In order to further dissect the cellular function of these gene products, we are seeking for capable post-doctoral researchers specialized in protein biochemistry and cellular signaling.

Yoshihiro Urade Lab You have a chance to make a breakthrough in the science of sleep, the most mysterious animal behavior.

We spend about 1/3 to 1/4 of our lives asleep. If our sleep is restricted, our brain does not function normally. Everybody is aware of this fact. However, nobody knows its precise reason. We are able to induce sleep in experimental animals anytime we want to study sleep, by using endogenous sleep substances, such as prostaglandin D2 and adenosine. We established the sleep bioassay system for experimental animals, by monitoring their brain waves. In combination with modern gene-manipulation and neuroscience technologies, we investigate the molecular mechanism and the neural circuits of sleep-wake regulation. Scientific sleep research has a limited history of only 1 century. Therefore, sleep science is a new frontier with many unanswered questions. You have so many chances to make great discoveries in this field. Join us as we pursue new answers to the questions of sleep science together. Mystery and excitement await you in our lab.

Hiroshi Nagase Lab Let’s develop first-in-class drugs through advanced medicinal chemistry.
“You can also release original new drugs for intractable disease patients.”

We are a group of medicinal chemists who can design and synthesize receptor selective ligands. However, we don’t believe that so many real medicinal chemists exist in Japan. Therefore, we can offer to change you into a medicinal chemist if you are an expert of synthetic organic chemistry. If you are a hard worker, you have only to work with us by using organic chemistry, which will lead you to become an excellent medicinal chemist. Our target molecules are orexin receptor agonists for narcolepsy patients. We also try to clarify the mechanism for narcolepsy using opioid ligands. Opioids were known to interact with not only dopamine, serotonin and norepinephrine receptors, but also the orexin receptor. We have many opioid type selective ligands. Using the ligands, we will study the interaction of the orexin receptor with the opioid receptor to clarify the mechanism of narcolepsy. If you are interested in our studies, please contact us. We are looking forward to hearing from you.

Takeshi Sakurai / Masanori Sakaguchi Lab This is the place if you’re looking for sleep and memory.

Our lab utilizes the most advanced techniques (e.g., optogenetics, in vivo brain activity recordings, neural circuit imaging, etc.) to elucidate the relation between sleep and memory. We are currently comprised of 7 lab members with diverse biological backgrounds and experimental expertise, including 2 medical students. Prof. Sakurai, a specialist in sleep research renowned for his discovery of the neuropeptide orexin, along with Dr. Sakaguchi are the group heads of our lab. Dr. Sakaguchi holds numerous papers (9 first authors and 16 co-authorships in international journals), speaks fluent English, intermediate-level Chinese, and can relate to both Western and Asian cultures. We are looking for bright and motivated students (full-ride scholarships available) from all over the world to join our lab and help us tackle this exciting field.

Michael Lazarus Lab Molecular Systems Sleep Biology

We aim to explore the role of motivation-related neuronal pathways in facilitating wakefulness by using a new generation of powerful tools for the site-specific gene knockout, such as conditional knockout mice based on the Cre/lox technology and local infection with adeno-associated virus carrying RNA interference, and the modulation of neuronal activity through in-vivo stimulation and inhibition [e.g., designer receptors exclusively activated by a designer drug (DREADD), ivermectin-gated chloride channels, or optogenetics], all in combination with a high-throughput sleep bioassay system. Other research in the laboratory includes elucidating striatal adenosine A2A receptors or striatopallidal neurons as therapeutic target in the treatment of sleep disturbance and cognitive impairment in Parkinson Disease and identifying the anatomical substrate and the molecular components of methamphetamine-sensitive circadian oscillation.

Yu Hayashi Lab Molecular and evolutionary basis of REM and non-REM sleep

Our lab has two major themes: 1. elucidation of the individual roles and evolutionary origins of REM and non-REM sleep using mice, and 2. identification of widely conserved molecular mechanisms underlying sleep using the nematode C. elegans. To this end, we will combine pharmacogenetic or optogenetic approaches with behavioral studies, neuronal recording studies, or imaging studies. Lab members are expected to be either familiar with these techniques or highly motivated to acquire them. In addition, to gain a broad insight, we expect that all lab members be engaged in both the mouse and nematode projects.

Qinghua Liu Lab Integrating genetic, biochemical, and chemical biology approaches to uncover the molecular circuit of sleep regulation and open new avenues to develop future sleep medicine.

Sleep is essential for normal brain functions and viability in mammals, however, the molecular circuits of sleep regulation remains a fundamental mystery in modern biology. My laboratory will integrate biochemical, chemical biology, and genetic approaches to identify key genes in sleep/wake regulation in mice: 1) We will use the state-of-the-art quantitative mass spectrometry (e.g. SILAC) to compare brain proteome between wild type and sleep mutant mice, isolated from a forward genetic screen, to identify candidate sleep regulatory genes; 2) We will develop a novel and rapid technology for adult- and brain-specific knockdown (or knockout) of candidate genes to investigate their functions in sleep/wake regulation; 3)We will conduct in vivo screening of natural or synthetic small molecules to identify sleep-promoting compounds. Together, these multi-disciplinary studies will uncover novel mechanism of sleep regulation and develop novel sleep medicine.

Robert Greene Lab Cellular, synaptic and local circuit mechanisms generating slow wave activity

Slow wave activity (SWA) power expressed during slow wave sleep (SWS) increases proportionally with prior waking duration and decays during SWS. This large circuit phenomena is the most robust index of sleep need currently available, yet little is known about the local circuit and cellular activities that are responsible for its generation. Further, it has been proposed that the up states occurring during SWS are electrophysiologically identical to stabilized up state membrane potentials during waking (W) and that SWA reflects a destabilized up state, but this has not been rigorously investigated. We plan to employ whole cell patch clamp recordings of cortical, pyramidal cells and interneurons acquired in vivo in un-anesthetized rodents during W and SWS, in conjunction with local field recordings, imaging of intracellular free calcium concentration and optogenetically controlled activation of distinct morphological subsets of interneurons to investigate the local network and cellular mechanisms involved in SWA generation.

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