Dmitri Nusinow

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Dmitri Nusinow is an American chronobiologist who studies plant circadian rhythms. [1] He was born on November 7, 1976, in Inglewood, California. He currently resides in St. Louis, and his research focus includes a combination of molecular, biochemical, genetic, genomic, and proteomic tools to discover the molecular connections between signaling networks, circadian oscillators, and specific outputs. By combining these methods, he hopes to apply the knowledge elucidated from the Arabidopsis model to other plant species.

Contents

Education and career

Nusinow received his bachelor's degree in Microbiology and Molecular Genetics at University of California Los Angeles (UCLA) in 1998. During his undergraduate years, Nusinow worked in Jay Gralla's lab and studied in vitro analysis of RNA Pol II transcription in the fission yeast, S.pombe . [2] He continued his education to earn his PhD in Biochemistry and Molecular Biology at University of California San Francisco (UCSF) from 1999 to 2006. During his first four years of graduate school, Nusinow attempted to create a quadruple knock-in (KI) mouse that would purify the protein RNA complex of X-inactive specific transcript (Xist), which plays a key role in dosage compensation in female mammals. The method was unsuccessful, so Nusinow shifted his focus on the mammalian histone variant macroH2A. He discovered that the inhibition of PARP1 by macro-H2A1 contributed to X chromosome inactivation. [3] While in graduate school, he attended a seminar by Roger Hangarter who showed circadian regulated movements in sunflowers. [4] This seminar inspired Nusinow to switch and study circadian rhythms in plants. In 2007, he became a researcher at the Scripps Institute with Steve Kay, and continued with the lab when it moved to University of California San Diego (UCSD) for five additional years. [5] While in Kay's lab, he was influenced by fellow researcher Takato Imaizumi to study ELF3 in plants. Nusinow then became a principal investigator at the Donald Danforth Plant Science Center and an adjunct professor at Washington University in St. Louis in 2012. [6] He now studies to understand how the circadian clock is integrated with environmental signals to control growth, development, and physiology in order to improve the productivity in plants.

Scientific contributions to circadian rhythms in Arabidopsis

Photosensitivity of FKF1/GI complex

In 2007, Sawa, Nusinow, Kay, and Imaizumi identified how Arabidopsis proteins FKF1 (Flavin-binding, Kelch repeat, F-box 1) and GI (Gigantea) helped regulate flowering photoperiods in Arabidopsis. [7] Their interest in these proteins arose when they saw FKF1 and GI had displayed similar peak times of expression during the long days. [7] Subsequently, they isolated Arabidopsis proteins FKF1 and GI in a test tube and showed that blue light induced in vitro formation of FKF1 and GI complex. [7] The blue light was absorbed by the LOV (Light, Oxygen, or Voltage) domain on the FKF1 protein, and the N terminus of the GI protein was sufficient to interact with FKF1. [7] To test whether the proteins interacted in vivo, they did a series of transgenic experiments on Arabidopsis. A two-hybrid screening method with HA (haemagglutinin)-tagged FKF1 and tandem affinity purification (TAP)-tagged GI system was used to show that GI and FKF1 formed a complex in vivo. [7] Additionally, they saw that this complex positively regulated daytime transcription of constans (CO), a gene promoting flowering in plants. [7] Their results led to a model of how FKF1 and GI complex regulated flowering in response to photoperiods in Arabidopsis.

Hypocotyl growth linked to ELF4/ELF4/LUX complex

Nusinow continued working with Arabidopsis and in 2011 as part of a team, he published a paper in the journal Nature where he identified proteins Early Flowering 4 (ELF4), Early Flowering 3 (ELF3), and gene lux arrhythmo (LUX) form a multi-protein clock complex that directly regulated growth in Arabidopsis. [8] [9] Proteins ELF3 and ELF4 contain basic helix-loop-helix (bHLH) structural motif that binds the proteins to DNA. [8] Nusinow named the ELF4, ELF3, and LUX complex “evening complex (EC)” after identifying the complex peaked at dusk. [8] Through a series of transgenic experiments, he showed that ELF4, ELF3, and LUX were required for proper expression of Phytochrome interacting Factor 4 (PIF4) and phytochrome interacting factor 5 (PIF5), two transcription factors critical for regulating hypocotyl growth Arabidopsis seedlings. [8]

Discovery of PCH1

In 2015 through 2016, Nusinow and his colleagues identified a protein that was repeatedly associated with the evening complex in AP-MS analysis of the plant circadian clock. Nusinow found that the protein, which he named PCH1 (Photoperiodic Control of Hypocotyl), was an important regulator for the growth of the hypocotyl (the stem of a seedling) during germination. PCH1 reduces hypocotyl growth during long nights by preferentially binding and stabilizing the active form of phytochrome B (phyB), prolonging its activity. [10] PhyB in turn forms photobodies in the nucleus, where it interacts with molecules of the evening complex (EC) to cause downstream inhibition of hypocotyl growth.

The discovery and characterization of PCH1 is especially notable because phyB is normally active only during the day. By stabilizing phyB and maintaining its signaling well into the night, PCH1 allows plant cells to “remember” past illumination and adjust growth programs accordingly.[ citation needed ]

Selected publications

Personal life

Nusinow currently resides in St. Louis with his wife and two children.

See also

Related Research Articles

In developmental biology, photomorphogenesis is light-mediated development, where plant growth patterns respond to the light spectrum. This is a completely separate process from photosynthesis where light is used as a source of energy. Phytochromes, cryptochromes, and phototropins are photochromic sensory receptors that restrict the photomorphogenic effect of light to the UV-A, UV-B, blue, and red portions of the electromagnetic spectrum.

Photoperiodism is the physiological reaction of organisms to the length of night or a dark period. It occurs in plants and animals. Plant photoperiodism can also be defined as the developmental responses of plants to the relative lengths of light and dark periods. They are classified under three groups according to the photoperiods: short-day plants, long-day plants, and day-neutral plants.

Shade avoidance is a set of responses that plants display when they are subjected to the shade of another plant. It often includes elongation, altered flowering time, increased apical dominance and altered partitioning of resources. This set of responses is collectively called the shade-avoidance syndrome (SAS).

<span class="mw-page-title-main">Cryptochrome</span> Class of photoreceptors in plants and animals

Cryptochromes are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields in a number of species. The name cryptochrome was proposed as a portmanteau combining the chromatic nature of the photoreceptor, and the cryptogamic organisms on which many blue-light studies were carried out.

Florigens are proteins capable of inducing flowering time in Angiosperms. The prototypical florigen is encoded by the FT gene and its orthologs in Arabidopsis and other plants. Florigens are produced in the leaves, and act in the shoot apical meristem of buds and growing tips.

The repressilator is a genetic regulatory network consisting of at least one feedback loop with at least three genes, each expressing a protein that represses the next gene in the loop. In biological research, repressilators have been used to build cellular models and understand cell function. There are both artificial and naturally-occurring repressilators. Recently, the naturally-occurring repressilator clock gene circuit in Arabidopsis thaliana and mammalian systems have been studied.

Timing of CAB expression 1 is a protein that in Arabidopsis thaliana is encoded by the TOC1 gene. TOC1 is also known as two-component response regulator-like APRR1.

Circadian Clock Associated 1 (CCA1) is a gene that is central to the circadian oscillator of angiosperms. It was first identified in Arabidopsis thaliana in 1993. CCA1 interacts with LHY and TOC1 to form the core of the oscillator system. CCA1 expression peaks at dawn. Loss of CCA1 function leads to a shortened period in the expression of many other genes.

Steve A. Kay is a British-born chronobiologist who mainly works in the United States. Dr. Kay has pioneered methods to monitor daily gene expression in real time and characterized circadian gene expression in plants, flies and mammals. In 2014, Steve Kay celebrated 25 years of successful chronobiology research at the Kaylab 25 Symposium, joined by over one hundred researchers with whom he had collaborated with or mentored. Dr. Kay, a member of the National Academy of Sciences, U.S.A., briefly served as president of The Scripps Research Institute. and is currently a professor at the University of Southern California. He also served on the Life Sciences jury for the Infosys Prize in 2011.

Plants depend on epigenetic processes for proper function. Epigenetics is defined as "the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence". The area of study examines protein interactions with DNA and its associated components, including histones and various other modifications such as methylation, which alter the rate or target of transcription. Epi-alleles and epi-mutants, much like their genetic counterparts, describe changes in phenotypes due to epigenetic mechanisms. Epigenetics in plants has attracted scientific enthusiasm because of its importance in agriculture.

LUX or Phytoclock1 (PCL1) is a gene that codes for LUX ARRHYTHMO, a protein necessary for circadian rhythms in Arabidopsis thaliana. LUX protein associates with Early Flowering 3 (ELF3) and Early Flowering 4 (ELF4) to form the Evening Complex (EC), a core component of the Arabidopsis repressilator model of the plant circadian clock. The LUX protein functions as a transcription factor that negatively regulates Pseudo-Response Regulator 9 (PRR9), a core gene of the Midday Complex, another component of the Arabidopsis repressilator model. LUX is also associated with circadian control of hypocotyl growth factor genes PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and PHYTOCHROME INTERACTING FACTOR 5 (PIF5).

Andrew John McWalter Millar, FRS, FRSE is a Scottish chronobiologist, systems biologist, and molecular geneticist. Millar is a professor at The University of Edinburgh and also serves as its chair of systems biology. Millar is best known for his contributions to plant circadian biology; in the Steve Kay lab, he pioneered the use of luciferase imaging to identify circadian mutants in Arabidopsis. Additionally, Millar's group has implicated the ELF4 gene in circadian control of flowering time in Arabidopsis. Millar was elected to the Royal Society in 2012 and the Royal Society of Edinburgh in 2013.

Pseudo-response regulator (PRR) refers to a group of genes that regulate the circadian oscillator in plants. There are four primary PRR proteins that perform the majority of interactions with other proteins within the circadian oscillator, and another (PRR3) that has limited function. These genes are all paralogs of each other, and all repress the transcription of Circadian Clock Associated 1 (CCA1) and Late Elongated Hypocotyl (LHY) at various times throughout the day. The expression of PRR9, PRR7, PRR5 and TOC1/PRR1 peak around morning, mid-day, afternoon and evening, respectively. As a group, these genes are one part of the three-part repressilator system that governs the biological clock in plants.

Joanna Jean Putterill is a New Zealand molecular botanist. She is currently a full professor at the University of Auckland.

The Late Elongated Hypocotyl gene (LHY), is an oscillating gene found in plants that functions as part of their circadian clock. LHY encodes components of mutually regulatory negative feedback loops with Circadian Clock Associated 1 (CCA1) in which overexpression of either results in dampening of both of their expression. This negative feedback loop affects the rhythmicity of multiple outputs creating a daytime protein complex. LHY was one of the first genes identified in the plant clock, along with TOC1 and CCA1. LHY and CCA1 have similar patterns of expression, which is capable of being induced by light. Single loss-of-function mutants in both genes result in seemingly identical phenotypes, but LHY cannot fully rescue the rhythm when CCA1 is absent, indicating that they may only be partially functionally redundant. Under constant light conditions, CCA1 and LHY double loss-of-function mutants fail to maintain rhythms in clock-controlled RNAs.

Transcription-translation feedback loop (TTFL) is a cellular model for explaining circadian rhythms in behavior and physiology. Widely conserved across species, the TTFL is auto-regulatory, in which transcription of clock genes is regulated by their own protein products.

EARLY FLOWERING 3 (ELF3) is a plant-specific gene that encodes the hydroxyproline-rich glycoprotein and is required for the function of the circadian clock. ELF3 is one of the three components that make up the Evening Complex (EC) within the plant circadian clock, in which all three components reach peak gene expression and protein levels at dusk. ELF3 serves as a scaffold to bind EARLY FLOWERING 4 (ELF4) and LUX ARRHYTHMO (LUX), two other components of the EC, and functions to control photoperiod sensitivity in plants. ELF3 also plays an important role in temperature and light input within plants for circadian clock entrainment. Additionally, it plays roles in light and temperature signaling that are independent from its role in the EC.

Elaine Munsey Tobin is a professor of molecular, cell, and developmental biology at the University of California, Los Angeles (UCLA). Tobin is recognized as a Pioneer Member of the American Society of Plant Biologists (ASPB).

The chlorophyll a/b-binding protein gene, otherwise known as the CAB gene, is one of the most thoroughly characterized clock-regulated genes in plants. There are a variety of CAB proteins that are derived from this gene family. Studies on Arabidopsis plants have shed light on the mechanisms of biological clocks under the regulation of CAB genes. Dr. Steve Kay discovered that CAB was regulated by a circadian clock, which switched the gene on in the morning and off in the late afternoon. The genes code for proteins that associate with chlorophyll and xanthophylls. This association aids the absorption of sunlight, which transfers energy to photosystem II to drive photosynthetic electron transport.

Stacey Harmer is a chronobiologist whose work centers on the study of circadian rhythms in plants. Her research focuses on the molecular workings of the plant circadian clock and its influences on plant behaviors and physiology. She is a professor in the Department of Plant Biology at the University of California, Davis.

References

  1. ↑ "Scientists and Research". danforthcenter.org. Donald Danforth Plant Science Center. Retrieved 13 April 2017.
  2. ↑ Choi, Wai S.; Yan, Ming; Nusinow, Dmitri; Gralla, Jay D. (2002-06-21). "In Vitro Transcription and Start Site Selection in Schizosaccharomyces pombe". Journal of Molecular Biology. 319 (5): 1005–1013. doi:10.1016/S0022-2836(02)00329-7. PMID   12079343.
  3. ↑ Buschbeck, Marcus; Uribesalgo, Iris; Wibowo, Indra; Rué, Pau; Martin, David; Gutierrez, Arantxa; Morey, Lluís; Guigó, Roderic; López-Schier, Hernán (2009-10-01). "The histone variant macroH2A is an epigenetic regulator of key developmental genes". Nature Structural & Molecular Biology. 16 (10): 1074–1079. doi:10.1038/nsmb.1665. ISSN   1545-9993. PMID   19734898. S2CID   11920448.
  4. ↑ "Plants-In-Motion Home". plantsinmotion.bio.indiana.edu. Retrieved 2017-04-27.
  5. ↑ "UCSD Center for Chronobiology 5 year review" (PDF).
  6. ↑ "Ask A Plant Scientist: Dmitri Nusinow, PH.D." www.danforthcenter.org. Retrieved 2017-04-27.
  7. 1 2 3 4 5 6 7 Sawa, Mariko; Nusinow, Dmitri A.; Kay, Steve A.; Imaizumi, Takato (2007-10-12). "FKF1 and GIGANTEA Complex Formation Is Required for Day-Length Measurement in Arabidopsis". Science. 318 (5848): 261–265. Bibcode:2007Sci...318..261S. doi:10.1126/science.1146994. ISSN   0036-8075. PMC   3709017 . PMID   17872410.
  8. 1 2 3 4 5 Nusinow, Dmitri A.; Helfer, Anne; Hamilton, Elizabeth E.; King, Jasmine J.; Imaizumi, Takato; Schultz, Thomas F.; Farré, Eva M.; Kay, Steve A. (2011). "The ELF4–ELF3–LUX complex links the circadian clock to diurnal control of hypocotyl growth". Nature. 475 (7356): 398–402. doi:10.1038/nature10182. PMC   3155984 . PMID   21753751.
  9. ↑ "'Evening complex' proteins help corn grow taller at night". Farm Industry News. 2011-07-18. Retrieved 2017-04-28.
  10. 1 2 Huang, He; Yoo, Chan Yul; Bindbeutel, Rebecca; Goldsworthy, Jessica; Tielking, Allison; Alvarez, Sophie; Naldrett, Michael J.; Evans, Bradley S.; Chen, Meng; Nusinow, Dmitri (2016-02-03). "PCH1 integrates circadian and light-signaling pathways to control photoperiod-responsive growth in Arabidopsis". eLife. 5: e13292. doi:10.7554/eLife.13292. ISSN   2050-084X. PMC   4755757 . PMID   26839287.
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