Jennifer Loros

Last updated
Jennifer Loros
Born15 April 1950
San Mateo, California
NationalityAmerican
Other namesJJ Loros
SpouseJay Dunlap
AwardsNational Science Foundation Merit Award and Creativity Award, Aschoff's Ruler
Scientific career
FieldsChronobiology, Biochemistry, Cell Biology, Molecular and Systems Biology

Jennifer Loros, also known as J.J. Loros, is a chronobiologist leading the field in the study of circadian rhythms in Neurospora . Her research focuses on circadian oscillators and their control of gene expression in living cells. Currently, Loros is a professor of Biochemistry, Cell Biology, and Molecular and Systems Biology at the Giesel School of Medicine. [1]

Contents

Biography

Education

Loros is from Los Altos, California. She attended Homestead High School and graduated in 1968. Loros then attended both Cabrillo College and Monterey Peninsula College and received two associate degrees in Biology by 1971. [2]

By 1979, Loros received her bachelor's degree in Biology from UC Santa Cruz. She went on to complete her PhD in Genetics from Dartmouth Medical School. [1]

Career (1988-present)

In 1988, Loros began her career in biology at Dartmouth Medical School as a postdoctoral researcher in Biochemistry. [2] By 1994, Loros earned the position of Research Associate Professor of Biochemistry [2] and then accepted the position of Associate Professor of Biochemistry in 1996. She then became Professor of Biochemistry and Professor of Genetics in 2000 and 2001 respectively. [1]

Loros also leads research at the Dunlap and Loros Laboratories with her husband Jay Dunlap, a fellow chronobiologist and researcher. [2] Her focus is on the circadian clock in Neurospora and its application to the genetic mechanisms of the clock in other organisms. [1] [2] Loros, along with Jay Dunlap and Patricia J. DeCoursey, co-authored the text book "Chronobiology: Biological Timekeeping " which was published on June 1, 2004. The text chronicles the field of chronobiology by exploring both past and current discoveries and their relevance to modern society. [3]

Scientific career

Advancements in methodology

Dr. Loros contributed to advancing research techniques by developing a targeted gene disruption technique for use in Neurospora, which had the effect of amplifying gene markers in such a manner as to make identification of low homologous recombination rates possible, which had previously not been the case when using traditional techniques such as Southern Blot tests. [4] Gene identification in Neurospora was additionally progressed by Loros’ lab when it produced a high density SNP map for Neurospora . [4] [5]

Lastly, continuing on with an idea from her post-doc work, Loros resynthesized a gene that codes for firefly luciferase. [2] Since Neurospora has long been a key model organism in the chronobiology field, modifying this tool has been key in further research. Before this, codon bias prevented effective usage of firefly luciferase in Neurospora, problematic as firefly luciferase serves as a reporter to measure transcription in cells. By modifying the firefly luciferase gene, Loros was able to achieve several orders more of light production in Neurospora , revolutionizing transcription measurements in N. cell cultures. Moreover, her modification to this reporter allowed the   FRQ/WCC feedback loop to be monitored in real time without disturbing the overt rhythms of the system. This in turn provided the tool to distinguish between oscillators not directly in the clock and the circadian clock itself. [6]

Research into clock-controlled genes and frq

After joining the faculty of the Giesel School of Medicine, Loros continued her post-doc research into the regulation of messenger RNA by circadian clocks. [7] Through sequential rounds of subtractive hybridization, Loros found 2 such genes that are responsible for transcription in morning specific cultures of Neurospora . Loros named these two, unlinked, genes ccg-1 and ccg-2, with the initialisms standing for clock-controlled genes, a term which, now prevalent in the circadian clock dialogue, Loros claims to have coined herself. [2] [7] Moreover, her work on the negative feedback loop involved in the FRQ pathway demonstrated that the phosphorylation of negative elements of the clock are not as important in controlling the period as once thought. Loros and her collaborators showed that the nature of the FRQ allele controlled the pace of the clock, not the rate of phosphorylation and degradation of clock elements.

Research into photobiology, the White-Collar Complex, and Aspergillus Fumigatus

During her post-doc work, Loros remarked upon the possibility of frq being light induced, which was later confirmed by a post-doc fellow. [8] Turning her attention to the governing body for this light induction, Loros began experimenting with wc-1 finding that it not only was the mediator for said light induction, but was also necessary for Neurospora’s clock in the absence of light. [8]

Wc-1, in conjunction with its partner protein, wc-2, was found to be the first described positive element regulator in a circadian feedback loop, with the norm being that of negative regulators. This led to the precedent of the PAS-PAS heterodimers in both animals and fungi alike. [8]

The role of metabolism in the circadian system

Recently, Loros has worked on examining the reciprocal relationship between metabolism and circadian rhythm. Using Neurospora as her model organism, Loros’ work has revealed how interconnected these two crucial systems are in fungi. These links include both the outputs of each system and how metabolism can directly influence the rhythms set by the clock. [9]

Related Research Articles

<i>Neurospora crassa</i> Species of ascomycete fungus in the family Sordariaceae

Neurospora crassa is a type of red bread mold of the phylum Ascomycota. The genus name, meaning 'nerve spore' in Greek, refers to the characteristic striations on the spores. The first published account of this fungus was from an infestation of French bakeries in 1843.

In molecular biology, an oscillating gene is a gene that is expressed in a rhythmic pattern or in periodic cycles. Oscillating genes are usually circadian and can be identified by periodic changes in the state of an organism. Circadian rhythms, controlled by oscillating genes, have a period of approximately 24 hours. For example, plant leaves opening and closing at different times of the day or the sleep-wake schedule of animals can all include circadian rhythms. Other periods are also possible, such as 29.5 days resulting from circalunar rhythms or 12.4 hours resulting from circatidal rhythms. Oscillating genes include both core clock component genes and output genes. A core clock component gene is a gene necessary for to the pacemaker. However, an output oscillating gene, such as the AVP gene, is rhythmic but not necessary to the pacemaker.

Bacterial circadian rhythms, like other circadian rhythms, are endogenous "biological clocks" that have the following three characteristics: (a) in constant conditions they oscillate with a period that is close to, but not exactly, 24 hours in duration, (b) this "free-running" rhythm is temperature compensated, and (c) the rhythm will entrain to an appropriate environmental cycle.

The frequency (frq) gene encodes the protein frequency (FRQ) that functions in the Neurospora crassa circadian clock. The FRQ protein plays a key role in circadian oscillator, serving to nucleate the negative element complex in the auto regulatory transcription-translation negative feedback-loop (TTFL) that is responsible for circadian rhythms in N. crassa. Similar rhythms are found in mammals, Drosophila and cyanobacteria. Recently, FRQ homologs have been identified in several other species of fungi. Expression of frq is controlled by the two transcription factors white collar-1 (WC-1) and white collar-2 (WC-2) that act together as the White Collar Complex (WCC) and serve as the positive element in the TTFL. Expression of frq can also be induced through light exposure in a WCC dependent manner. Forward genetics has generated many alleles of frq resulting in strains whose circadian clocks vary in period length.

Till Roenneberg is a professor of chronobiology at the Institute of Medical Psychology at Ludwig-Maximilian University (LMU) in Munich, Germany. Roenneberg, in collaboration with Martha Merrow, explores the impact of light on human circadian rhythms, focusing on aspects such as chronotypes and social jet lag in relation to health benefits.

A Light-oxygen-voltage-sensing domain is a protein sensor used by a large variety of higher plants, microalgae, fungi and bacteria to sense environmental conditions. In higher plants, they are used to control phototropism, chloroplast relocation, and stomatal opening, whereas in fungal organisms, they are used for adjusting the circadian temporal organization of the cells to the daily and seasonal periods. They are a subset of PAS domains.

<span class="mw-page-title-main">Jeffrey C. Hall</span> American geneticist and chronobiologist (born 1945)

Jeffrey Connor Hall is an American geneticist and chronobiologist. Hall is Professor Emeritus of Biology at Brandeis University and currently resides in Cambridge, Maine.

<span class="mw-page-title-main">Takao Kondo</span>

Takao Kondo is a Japanese biologist and professor of biological science at Nagoya University in Nagoya, Japan. He is best known for reconstituting the circadian clock in vitro.

White Collar-1 (wc-1) is a gene in Neurospora crassa encoding the protein WC-1. WC-1 has two separate roles in the cell. First, it is the primary photoreceptor for Neurospora and the founding member of the class of principle blue light photoreceptors in all of the fungi. Second, it is necessary for regulating circadian rhythms in FRQ. It is a key component of a circadian molecular pathway that regulates many behavioral activities, including conidiation. WC-1 and WC-2, an interacting partner of WC-1, comprise the White Collar Complex (WCC) that is involved in the Neurospora circadian clock. WCC is a complex of nuclear transcription factor proteins, and contains transcriptional activation domains, PAS domains, and zinc finger DNA-binding domains (GATA). WC-1 and WC-2 heterodimerize through their PAS domains to form the White Collar Complex (WCC).

Hitoshi Okamura 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 Science Technology Institute, CREST. Okamura's research group cloned mammalian Period genes, visualized clock oscillation at the single cell level in the central clock of the SCN, and proposed a time-signal neuronal pathway to the adrenal gland. He received a Medal of Honor with Purple Ribbon in 2007 for his research and was awarded Aschoff's Ruler for his work on circadian rhythms in rodents. His lab recently revealed the effects of m6A mRNA methylation on the circadian clock, neuronal communications in jet lag, and the role of dysregulated clocks in salt-induced hypertension.

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.

<span class="mw-page-title-main">Carl H. Johnson</span> American-born biologist

Carl Hirschie Johnson is an American-born biologist who researches the chronobiology of different organisms, most notably the bacterial circadian rhythms of cyanobacteria. Johnson completed his undergraduate degree in Honors Liberal Arts at the University of Texas at Austin, and later earned his PhD in biology from Stanford University, where he began his research under the mentorship of Dr. Colin Pittendrigh. Currently, Johnson is the Stevenson Professor of Biological Sciences at Vanderbilt University.

The white collar--2 (wc-2) gene in Neurospora crassa encodes the protein White Collar-2 (WC-2). WC-2 is a GATA transcription factor necessary for blue light photoreception and for regulating circadian rhythms in Neurospora. In both contexts, WC-2 binds to its non-redundant counterpart White Collar-1 (WC-1) through PAS domains to form the White Collar Complex (WCC), an active transcription factor.

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References

  1. 1 2 3 4 "Faculty : Department of Molecular and Systems Biology :: Geisel School of Medicine". geiselmed.dartmouth.edu. Retrieved 2017-04-13.
  2. 1 2 3 4 5 6 7 "Geisel School of Medicine :: Dunlap - Loros Lab :: Lab Members". geiselmed.dartmouth.edu. Retrieved 2017-04-13.
  3. ↑ Giebultowicz, Jadwiga (2004). "Chronobiology: Biological Timekeeping". Integrative and Comparative Biology. 44 (3): 266. doi:10.1093/icb/44.3.266. PMID   21676707 . Retrieved 2017-04-30.
  4. 1 2 Dunlap, J. C., K. A. Borkovich, M. R. Henn, G. E. Turner, M. S. Sachs, N. L. Glass, K. McCluskey, M. Plamann, J. E. Galagan, B. W. Birren, R. L. Weiss, J. P. Townsend, J. J. Loros, M. A. Nelson, R. Lambreghts, H. V. Colot, G. Park, P. Collopy, C. Ringelberg, C. Crew, L. Litvinkova, D. DeCaprio, H. M. Hood, S. Curilla, M. Shi, M. Crawford, M. Koerhsen, P. Montgomery, L. Larson, M. Pearson, T. Kasuga, C. Tian, M. Baştürkmen, L. Altamirano, and J. Xu. (2007). "Enabling a Community to Dissect an Organism: Overview of the Neurospora Functional Genomics Project." Advanced Genetics. Advances in Genetics. 57: 490–49449–96. doi:10.1016/S0065-2660(06)57002-6. ISBN   9780120176571. PMC   3673015 . PMID   17352902.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ↑ Dekhang, Rigzin; Cheng Wu; Kristina M. Smith; Teresa M. Lamb; Matthew Peterson; Erin L. Bredeweg; Oneida Ibarra; Jillian M. Emerson; Nirmala Karunarathna; Anna Lyubetskaya; Elham Azizi; Jennifer M. Hurley; Jay C. Dunlap; James E. Galagan; Michael Freitag; Matthew S. Sachs; Deborah Bell-Pedersen (January 2017). "The Neurospora Transcription Factor ADV-1 Transduces Light Signals and Temporal Information to Control Rhythmic Expression of Genes Involved in Cell Fusion". Genetics. 7 (1): 129–142. doi:10.1534/g3.116.034298. PMC   5217103 . PMID   27856696.
  6. ↑ Fiedler, M. R., T. Gensheimer, C. Kubisch, and V. Meyer. (8 March 2017). "HisB as Novel Selection Marker for Gene Targeting Approaches in Aspergillus Niger". BMC Microbiology. 17 (1): 57. doi:10.1186/s12866-017-0960-3. PMC   5343542 . PMID   28274204.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. 1 2 Aronson, B. D., K. A. Johnson, Q. Liu, and J. C. Dunlap. (June 1992). "Molecular Analysis of the Neurospora Clock: Cloning and Characterization of the Frequency and Period-4 Genes". Chronobiology International. 9 (3): 231–239. doi:10.3109/07420529209064532. PMID   1535290.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. 1 2 3 Brunner, M., and T. Schafmeier. (1 May 2006). "Transcriptional and Post-transcriptional Regulation of the Circadian Clock of Cyanobacteria and Neurospora". Genes & Development. 20 (9): 1061–1074. doi:10.1101/gad.1410406. PMID   16651653.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ↑ Montenegro-Montero, A., P. Canessa, and L. F. Larrondo. (2015). "Around the Fungal Clock: Recent Advances in the Molecular Study of Circadian Clocks in Neurospora and Other Fungi". Advances in Genetics. 92: 107–184. doi:10.1016/bs.adgen.2015.09.003. PMID   26639917.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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