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Emi Nagoshi

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Emi Nagoshi is an associate professor at the University of Geneva working in neurology and chronobiology. Her most renowned work includes discovering circadian oscillators in vitro cultured fibroblasts and observing distinct expression periods of the fibroblast circadian gene in different individuals[1]. Her other contributions are related to gene expression of drosophila pdf (PDF), a circadian neuropeptide, and genome-wide analysis for biological rhythms.

Background/Personal Life

Emi Nagoshi was born in Japan. She received a BS in Biology at Tohoku University from 1990-1994. She then received a PhD in medical science at Osaka University from 1994-2000 where she researched nucleocytoplasmic transport of macromolecules[2][3] and worked alongside DNAVEC Crop. to create a novel gene therapy vector prototype.[4] Nagoshi continued as a Postdoctoral fellow at University of Geneva in the laboratory of Ueli Schibler from 2001-2004 where she started studying circadian rhythms in mammalian cells. Here she developed a live-cell imaging technique to monitor circadian rhythms at single cell levels. The technique enabled her to examine relationships between cell division cycles and circadian rhythms in animal cells. She became a postdoctoral fellow at Howard Hughes Medical Institute at Brandeis University under supervisor Michael Rosbash where she continued studying circadian rhythms in the neural mechanisms of Drosophila melanogaster[1].

Research/Academic Career

Following her education, she became a Group Leader at the University of Bern in Switzerland from 2009-2013. Nagoshi then returned to the University of Geneva to work as an assistant professor from 2013-2018 and continued as a full-time associate professor from 2018 to the present date[5].

Dr. Nagoshi is currently an associate professor at the University of Geneva in the Department of Genetics and Evolution, focusing specifically on behavioral neuroscience and neurodegeneration. Dr. Nagoshi's work centers on the circadian clock, neurodegeneration, and the connection thereof. Her most recent publication is titled "The utility and caveat of split-GAL4s in the study of neurodegeneration"[6] co-authored with Dr. Luca Stickley and Rafael Koch.

Scientific findings

In 2001, Dr. Nagoshi began studying circadian rhythm and its gene expression, as well as circadian gene expression in individual fibroblasts. During this early period, Nagoshi focused her research on the properties and regulations of mammalian circadian timing systems. This research centered around the suprachiasmatic nuclei and its function as a master pacemaker, synchronizing subsidiary oscillators in peripheral tissues. As an author on paper Chromosoma by Gachon et al.[7], Nagoshi reviewed previous works on this model – which was previously accepted, but pointed out the inconsistencies regarding rhythm generation.

Circadian Oscillators in Fibroblasts

Her most well-known work was published in 2004, in which she discovered that in vitro cultured fibroblasts have circadian oscillators as robust as those in SCN neurons[1]. This was an unexpected finding as previous works had assumed only the central oscillator inside SCN neurons are self-sustained, while peripheral oscillators were not. However, Nagoshi's study demonstrated that in vitro NIH-3T3 mouse fibroblasts have robust cell-autonomous and self-sustained oscillators[8]. Furthermore, the study found circadian gene expression persisted in dividing cells, meaning that the circadian cycle is passed on to daughter cells.

Nagoshi continued her research on mammalian fibroblasts the next year, contributing to a study on the period length of fibroblast circadian gene expressions in humans. In this study conducted by Steve Brown, Dr. Nagoshi collaborated with him to find that this period length varies widely among individuals, specific to each person and varying with genotype[9]. This helped establish that the circadian clock is quite heterogeneous at the genetic level, suggesting a genetic origin for the variation.

Drosophila Circadian Behavior

In more recent years, Nagoshi has focused on working with drosophila models. Her study in 2010 focused on profiling gene expression in different subgroups of clock neurons in Drosophila melanogaster. She has pioneered a method to isolate and profile a small number of Drosophila brain neurons[10], which was later used to molecularly characterize ventral lateral neurons of drosophila, which are known to make contributions related to circadian behavior. Neurons were separately purified based on size as well as PDF expression, and their mRNA profiles were compared. The study revealed that RNA cycling and a surprising large fraction of specific gene expression are central features of clock neuron function.

Golden Rules for Genome-scale Circadian Analyses

In 2017, Nagoshi collaborated with more than 70 co-authors under the great effort of the late Michael Hughes, on a paper discussing future considerations and guidelines to generate reproducible, sound, and useful genome-scale data, which could greatly further research on biological rhythms. Here, the authors proposed 3 "Golden Rules" for genome-scale circadian analyses.

  1. Never duplicate and concatenate data before running statistics
  2. Control for multiple testing
  3. Deposit your raw data into public repositories.

These rules are meant to help future studies account for the uncertainties of large-scale experiments in systems biology research. Additionally, the paper identified three potential key areas for methodological improvement:

  1. Standardize methods for analyzing rhythmic time series from the same individual, especially with data from humans.
  2. Devise a standard for statistically assessing the likelihood that a data series is not rhythmic.
  3. Develop and consistently apply methods for evaluation perturbation of rhythmic parameters, i.e, period, phase and amplitude.

Dr. Nagoshi has also emphasized the role of Drosophila circadian clocks throughout her work. In her paper co-authored with Anatoly Kozlov and Rafael Koch[11], they discovered that nitric oxide acts as a linkage between the circadian pacemaker and rhythmic locomotor activity. The paper also uncovers the perineurial glia as one of two subtypes that aid in creating a blood-brain barrier. This perineurial glia acts as the preeminent source of nitric oxide that aids in the regulation of the circadian locomotor. In another of her published works with Jaumoille et al.[12], Nagoshi discovered the importance of the E75 and UNF nuclear receptors in drosophila pacemakers. In flies without these receptors, there is no locomotor rhythm present – while when these are functional, they work together to promote CLK/CYC-mediated transcription.

References

  1. 1.0 1.1 1.2 "Group Emi Nagoshi - Department of Genetics & Evolution - University of Geneva". genev.unige.ch. Retrieved 2023-04-27.
  2. Nagoshi, Emi; Yoneda, Yoshihiro (2001-04-01). "Dimerization of Sterol Regulatory Element-Binding Protein 2 via the Helix-Loop-Helix-Leucine Zipper Domain Is a Prerequisite for Its Nuclear Localization Mediated by Importin β". Molecular and Cellular Biology. 21 (8): 2779–2789. doi:10.1128/mcb.21.8.2779-2789.2001. ISSN 1098-5549. PMC 86908. PMID 11283257.
  3. Lee, Soo Jae; Sekimoto, Toshihiro; Yamashita, Eiki; Nagoshi, Emi; Nakagawa, Atsushi; Imamoto, Naoko; Yoshimura, Masato; Sakai, Hiroaki; Chong, Khoon Tee; Tsukihara, Tomitake; Yoneda, Yoshihiro (2003-11-28). "The structure of importin-beta bound to SREBP-2: nuclear import of a transcription factor". Science. 302 (5650): 1571–1575. Bibcode:2003Sci...302.1571L. doi:10.1126/science.1088372. ISSN 1095-9203. PMID 14645851. Unknown parameter |s2cid= ignored (help)
  4. Nakanishi, M.; Akuta, T.; Nagoshi, E.; Eguchi, A.; Mizuguchi, H.; Senda, T. (April 2001). "Nuclear targeting of DNA". European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences. 13 (1): 17–24. doi:10.1016/s0928-0987(00)00203-7. ISSN 0928-0987. PMID 11292564.
  5. "iGE3 website - Nagoshi Group". www.unige.ch. Retrieved 2023-04-27.
  6. Stickley, Luca; Koch, Rafael; Nagoshi, Emi (December 2023). "The utility and caveat of split-GAL4s in the study of neurodegeneration". Fly. 17 (1): 2192847. doi:10.1080/19336934.2023.2192847. ISSN 1933-6942. PMC 10038051 Check |pmc= value (help). PMID 36959085 Check |pmid= value (help).
  7. Gachon, Frédéric; Nagoshi, Emi; Brown, Steven A.; Ripperger, Juergen; Schibler, Ueli (September 2004). "The mammalian circadian timing system: from gene expression to physiology". Chromosoma. 113 (3): 103–112. doi:10.1007/s00412-004-0296-2. ISSN 0009-5915. PMID 15338234. Unknown parameter |s2cid= ignored (help)
  8. "Emi Nagoshi". scholar.google.com. Retrieved 2023-04-27.
  9. Brown, Steven A.; Fleury-Olela, Fabienne; Nagoshi, Emi; Hauser, Conrad; Juge, Cristiana; Meier, Christophe A.; Chicheportiche, Rachel; Dayer, Jean-Michel; Albrecht, Urs; Schibler, Ueli (October 2005). "The period length of fibroblast circadian gene expression varies widely among human individuals". PLOS Biology. 3 (10): e338. doi:10.1371/journal.pbio.0030338. ISSN 1545-7885. PMC 1233413. PMID 16167846.
  10. Nagoshi, Emi; Sugino, Ken; Kula, Ela; Okazaki, Etsuko; Tachibana, Taro; Nelson, Sacha; Rosbash, Michael (January 2010). "Dissecting differential gene expression within the circadian neuronal circuit of Drosophila". Nature Neuroscience. 13 (1): 60–68. doi:10.1038/nn.2451. ISSN 1546-1726. PMC 3878269. PMID 19966839.
  11. Kozlov, Anatoly; Koch, Rafael; Nagoshi, Emi (2020-06-29). "Nitric oxide mediates neuro-glial interaction that shapes Drosophila circadian behavior". PLOS Genetics. 16 (6): e1008312. doi:10.1371/journal.pgen.1008312. ISSN 1553-7404. PMC 7367490 Check |pmc= value (help). PMID 32598344 Check |pmid= value (help).
  12. Jaumouillé, Edouard; Machado Almeida, Pedro; Stähli, Patrick; Koch, Rafael; Nagoshi, Emi (2015-06-01). "Transcriptional Regulation via Nuclear Receptor Crosstalk Required for the Drosophila Circadian Clock". Current Biology. 25 (11): 1502–1508. doi:10.1016/j.cub.2015.04.017. ISSN 0960-9822. PMC 4454776. PMID 26004759.



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