Hajime Tei (程肇, テイハジメ born March 1959)Japan Science and Technology Agency
''Researchmap'', is a Japanese neuroscientist specializing in the study of

chronobiology Chronobiology is a field of biology that examines timing processes, including periodic (cyclic) phenomena in living organisms, such as their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronobi ...

. He currently serves as a professor at the

Kanazawa University Kanazawa University ( ja, 金沢大学, Kanazawa Daigaku, abbreviated to ja, 金大, Kindai) is a Japanese national university in the city of Kanazawa, the capital of Ishikawa Prefecture. Founded in 1862, it was chartered as a university in 194 ...

Graduate School of Natural Science & Technology. He is most notable for his contributions to the discovery of the mammalian

period Period may refer to: Common uses * Era, a length or span of time * Full stop (or period), a punctuation mark Arts, entertainment, and media * Period (music), a concept in musical composition * Periodic sentence (or rhetorical period), a concept ...

genes, which he discovered alongside

Yoshiyuki Sakaki is a Japanese molecular biologist. He was the sixth president of Toyohashi University of Technology and an emeritus professor of the University of Tokyo. Sakaki was born in Nagoya. He received a bachelor's degree in biochemistry from the Universi ...

and

Hitoshi Okamura Hitoshi Okamura (born December 2, 1952) is a Japanese scientist who specializes in chronobiology. He is currently a Professor of Systems Biology at Kyoto University Graduate School of Pharmaceutical Sciences and the Research Director of the Japan ...

Career

Between 1991 and 1992, Tei was a fellow for the Fellowships of the Japan Society for Japanese Junior Scientists at the

University of Tokyo , abbreviated as or UTokyo, is a public research university located in Bunkyō, Tokyo, Japan. Established in 1877, the university was the first Imperial University and is currently a Top Type university of the Top Global University Project by ...

’s Institute of Medical Science. He later held the position of assistant professor (1992-2001) and associate professor (2001-2004). During his time as an assistant professor, Tei worked alongside Yoshiyuki Sakaki and Hitoshi Okamura to discover the mammalian period genes ''

Per1 The PER1 gene encodes the period circadian protein homolog 1 protein in humans. Function The PER1 protein is important to the maintenance of circadian rhythms in cells, and may also play a role in the development of cancer. This gene is a memb ...

'', ''

Per2 PER2 is a protein in mammals encoded by the ''PER2'' gene. ''PER2'' is noted for its major role in circadian rhythms. Discovery The ''per ''gene'' ''was first discovered using forward genetics in ''Drosophila melanogaster, Drosophilla melanoga ...

'', and ''

Per3 The PER3 gene encodes the period circadian protein homolog 3 protein in humans. PER3 is a paralog to the PER1 and PER2 genes. It is a circadian gene associate with delayed sleep phase syndrome in humans. History The Per3 gene was independently ...

''. They also discovered the mammalian

homolog In biology, homology is similarity due to shared ancestry between a pair of structures or genes in different taxa. A common example of homologous structures is the forelimbs of vertebrates, where the wings of bats and birds, the arms of prima ...

of the ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

'' gene ''

Timeless Timeless (or atemporal) or timelessness (or atemporality) may refer to: * Agelessness, the condition of being unaffected by the passage of time * Akal (Sikh term), timelessness in Sikhism * Eternity, timeless existence or infinite duration * Immo ...

.'' In 2004, Tei became the principal investigator of the Laboratory of Chronogenomics at Mitsubishi Kagaku Institute of Life Sciences. In 2009, he became a full professor at the Kanazawa University Graduate School of Natural Science & Technology, a position he currently serves to-date.

Awards

Hajime Tei received the 13th Tsukahara Memorial Award in 1999, and the Aschoff-Honma Prize for chronobiology in 2001.

Scientific contributions

Chronobiology

Discovery of mammalian ''Period'' genes

In 1997, Hajime Tei, Yoshiyuki Sakaki, and Hitoshi Okamura identified the human and mouse ''Per'' homologues of the ''Drosophila'' ''Per'' gene. They discovered that ''hPer'' (the human homolog of ''dPer'') and ''mPer'' (the mouse homolog of ''dPer'') encoded PAS-domain-containing

polypeptides Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

that are highly homologous to ''dPer''. They also found that ''mPer'' showed autonomous circadian oscillation in its expression in the suprachiasmatic nucleus (SCN) which acts as the primary circadian pacemaker in the mammalian brain. They were able to discover this by using a method called intra-module scanning-

polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...

(IMS-PCR), which allowed them to screen out short stretches of DNA sequences and isolate mammalian homologs of the ''Drosophila'' ''Per'' gene.

Identification of mammalian ''Timeless'' homolog

In 1998, Hajime Tei, in collaboration with other researchers, identified a mammalian homolog of the ''Drosophila timeless'' gene. During this research project, ''timeless'' was analyzed in the adult mouse SCN, but only weak oscillations were observed.

Discovery of circadian clocks in peripheral organs

Tei and Shin Yamazaki developed the first rodent model that was used to monitor circadian gene expression rhythms. This was done using a luciferase reporter gene expressed under the ''Per1''. In 2000, using their rodent model, they discovered the existence of circadian clocks in peripheral organs of mammals. This discovery led to the current understanding of mammalian circadian control as a multi-oscillatory system. He was also part of a team that discovered feeding cycles can entrain liver independently of the suprachiasmatic nucleus (SCN) and the light cycle.

Calcium flux in mammalian pacemaker neurons

In 2005, Tei, G. Lundkvist, Y. Kwak, E. Davis, and G. Block proposed that the molecular clock was linked to neurons' membrane potential via voltage-dependent regulation of Ca²⁺ influx, as well as secondary action of intracellular Ca²⁺ on gene transcription. Additionally, the same study found that removal of Ca²⁺ from the medium, as well as blocking the Ca²⁺ channels, stopped the SCN's circadian clock, while hyperpolarization of a K⁺ medium led to altered rhythms in the SCN.

Regulation of bone resorption by circadian clocks

In 2016, a research team that included Tei discovered that clock genes, most specifically ''

Bmal1 Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) or brain and muscle ARNT-Like 1 (BMAL1) is a protein that in humans is encoded by the gene on chromosome 11, region p15.3. It's also known as ''BMAL1'', ''MOP3'', and, less com ...

'' and ''

'', are rhythmically expressed in

osteoblast Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...

s to modulate the osteoblast-dependent regulation of

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...

ogenesis by regulating 1,25(OH)₂D₃-induced ''

Rankl Receptor activator of nuclear factor kappa- ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiati ...

'' expression in osteoblasts. Specifically for Bmal1, they found that Bmal1-deficient osteoblasts promote osteoclastogenesis. These findings could lead to future studies of RAR patterns and bone turnover markers.

Timeline of contributions

Applications of scientific contributions

Tei holds a

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A p ...

on a ''Per1'' promoter sequence that, when operably linked to another gene, will rhythmically promote its

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

. This promoter sequence allows for the creation of

transgenic A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...

animals that will be useful in studying circadian disorders and diseases. Additionally, pharmaceutical treatments for such diseases can be tested on transgenic animals with this specific promoter.

Collaborators

From early in his professional career to his work current projects, Tei has worked with many other chronobiologists. Specifically, he is listed as a recurring co-author with the following scientists: * Yoshiyuki Sakaki * Shin Yamazaki *

Gene D. Block Gene David Block (born August 17, 1948) is an American biologist who has served as the current and 6th chancellor of the University of California, Los Angeles since August 2007. Block has served as Provost (education), provost and professor of b ...

* Rika Numano *

Michael Menaker Michael Menaker (May 19, 1934 – February 14, 2021), was an American chronobiology researcher, and was Commonwealth Professor of Biology at University of Virginia. His research focused on circadian rhythmicity of vertebrates, including contribu ...

References

{{DEFAULTSORT:Tei, Hajime Chronobiologists 1959 births Living people Japanese neuroscientists University of Tokyo alumni Academic staff of Kanazawa University