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Christine Merlin

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Christine Merlin
File:Christine Merlin.jpgChristine Merlin.jpg Christine Merlin.jpg
Christine Merlin, chronobiologist, at Texas A&M University
Born (1980-09-24) September 24, 1980 (age 45)
Soues, Hautes-Pyrénées, France
🏳️ CitizenshipFrance
🎓 Alma mater
💼 Occupation
Known for
  • Monarch butterfly sun compass
  • Migratory physiology and behavior
  • Circadian clock mechanisms in moths and butterflies
🌐 Websitehttps://www.merlinlab.org/

Christine Merlin (born September 24, 1980) is a chronobiologist who primarily researches monarch butterfly migration and circadian systems. Merlin proved the existence of circadian clocks in the antennae of monarch butterflies, and investigated the use of antennae for navigation via sun-dependent orientation. As a member in the lab of Steven M. Reppert, she assisted in fully sequencing the genome of the monarch butterfly. She is an assistant professor of biology in the Department of Biology at Texas A&M University. In addition, she is on the faculty of both genetics and neuroscience, and is a member of the Center for Biological Clocks Research at Texas A&M University.

Biography

Early Life

Merlin grew up in the small village of Soues, located in the Pyrenees Mountains of southwest France. Her interest in biological clocks began in graduate school where she studied the roles of moth pheromones in locating mating partners. She reasoned that the timing of pheromone release by females and pheromone reception by males was just as important as the chemical nature of the pheromones themselves, and decided to dedicate her work to circadian rhythms from that point onward.

Education and career

Merlin received her BS in animal biology at Pierre and Marie Curie University in Paris, France in 2002. She continued her education at the university to receive her MS in invertebrate physiology in 2003. Merlin studied circadian control of olfactory rhythms in moths at the laboratory of Emmanuelle Jacquin-Joly and Martine Maibeche-Coisne in Versailles and received her PhD in insect physiology in 2006 from Pierre and Marie Curie University.[1] She moved to the United States in 2007 to begin postdoctoral research in molecular neuroethology in Steven M. Reppert’s lab at the University of Massachusetts Medical School, where she studied butterfly migration[2]. In 2013, she accepted a position as Assistant Professor in biology at Texas A&M University in 2013. She also joined as a member of the Center for Biological Clocks Research at Texas A&M University in 2013. In 2014, she was added as faculty in neuroscience and genetics.[1]

Since 2014, Merlin has been a member of the Society for Research on Biological Rhythms (SRBR)[1][3], and a participant in the Insect Genetic Technologies Research Coordination Network (IGTRCN). She was a symposium speaker at the 2010 SRBR meeting, and was a speaker at the IGTRCN Technical Workshop in 2015.[1]

Awards and honors

Previous Research

Identification of circadian clock in moth antennae

In 2007, Merlin found evidence for circadian clock in the antennae of the moth, Spodoptera littoralis. Using quantitative real-time polymerase chain reaction (qPCR), she found circadian fluctuations in the gene expression of Period (per), Cryptochrome-1 and -2 (cry1 and cry2) clock genes in both the antennae and the brain.[2][7] She found that cry2 and per transcripts fluctuated in phase with each other, which supported the hypothesis that CRY2 protein functions as a repressor in the transcriptional translational feedback loop (TTFL). The CRY2 protein acts to repress the transcription of the cry2 gene by a heterodimer of transcription factors, CLOCK and CYCLE.

Merlin also analyzed electroantennogram (EAG) readings, from which she found that antennal response to sex pheromones was circadian. However, these EAG rhythms were found to be in an inverse phase relationship with the moth’s behavioral rhythms. This finding opened up further questions of whether the olfactory system of S. littoralis is acutely sensitive to stimulation of the antennae, or if it is strictly controlled by circadian processing in the brain. This question has led to further research in the mechanisms behind the circadian control of olfaction.[8]

Role of antennae in sun-oriented migration of monarch butterflies

When monarch butterflies migrate southward in the fall, they orient themselves by aligning the position of the sun based on their perception of the time of day. In 2009, while working the Reppert Lab at University of Massachusetts Medical School, Merlin and Robert J. Gegear demonstrated that the antennae of the monarch butterfly were necessary for proper migratory orientation. It was previously believed that the time-compensated sun compass and circadian clock existed in the monarch butterfly's brain. Merlin demonstrated that the circadian clock mechanism exists in the antennae of the butterfly while the location of the sun compass exists in the central complex (CX), a structure found in the midbrain of insects.[9] In order to make this distinction, Merlin and Gegear removed the monarchs’ antennae and found that the butterflies could not detect the position of the sun. In addition, they covered the antennae with black paint and discovered that the light sensory input from the antennae was needed for proper migratory orientation. Merlin and colleagues recorded data by plotting the Rayleigh distributions of butterfly flight-directions of groups exposed to 12-h light:12-h dark light cycles (LD), and 6-hour shifted LD cycles. From their findings they concluded that the antennae, which were previously thought to be primarily odor detectors, are essential for the monarch butterfly’s ability to orient migration toward the south. They also found that the antennae contained circadian clocks that were independent from the central brain clock.  Upon removal of the antennae, the monarchs’ showed no change in the molecular cycles of the central clock. Antennae in vitro showed a persistence in self sustained rhythms of TIM protein expression in constant darkness, and showed oscillations in TIM protein abundance in a light-dark cycle. These experiments proved that antennal circadian clocks have light-entrainable, independent rhythms.[9][10][11]

The discovery of the role of antennae in sun-oriented migration has provided considerable insight in radar studies of insect flight, such as the relationship between circadian clocks in butterfly antennae and selection of favorable winds at high altitudes during migration.[12] In addition, studies have investigated the evolutionary components and ecological consequences of long-range migration of insects, including the use of a magnetic inclination compass when the time-compensated sun compass can not be used.[13] Identification of the circadian clock in monarch butterfly antennae and its distinction from the central complex has been cited in studies to determine the cellular basis of head direction and contextual cues, such as clock-based cues, in insects.[14] The discovery has also led Merlin to study a new and novel approach for monarch migration genomic access via TALEN and CRISPR/Cas9-mediated targeted mutagenesis.[15]

Monarch butterfly genome

In 2011, Merlin collaborated with Steven Reppert, Shuai Zhan, and Jeffrey L. Boore to produce a draft 273 Mb genome of the migratory monarch butterfly by using whole genome shotgun and next generation sequencing techniques. Within this genome, they found an estimated 16,866 protein coding genes that may be involved in the butterfly’s migratory behavior. Among the findings of the experiment, they identified genes that are a part of the inputs and central processing of the sun-oriented compass, molecular components of the monarch circadian clock, chemoreceptors that potentially may be important for migration as well as further molecular signatures of flight oriented behavior.[16][17][18] The sequencing of the monarch butterfly genome has provided insight into other genomic studies, including the identification of molecular evolution in herbivores, especially since the monarch genome allowed researchers to understand residues outside the 12-amino acid H1-H2 domain outside of ATPα in a cardenolide-sequestering insect,[19] and phylogenomic studies identifying relationships between butterflies and moths.[20]

Current Research

Identifying the genetic and epigenetic basis of migratory physiology and behavior

Merlin’s ultimate goal in this area of research is to identify candidate genes and regulatory sites, via reverse-genetic tools, to specify the total contribution of specific genes to the yearly migration of monarch butterflies. To reach this ultimate goal, the mechanism of circadian clock control of the photoperiodically-induced migration and epigenetic mechanisms determining the migratory mode of butterflies must be identified. Merlin is currently attempting to establish these components by using an integrated approach that combines genome-wide profiling of gene expression and of active gene cis-regulatory elements, reverse-genetics, and physiology and behavior. RNA sequencing and DNA sequencing assists in genome-wide profiling and CRISPR-mediated gene targeting is used for reverse-genetics.[21][16]

Determining the mechanisms and evolution of circadian repression

Circadian rhythms are driven by intracellular molecular mechanisms in animals that rely on TTFL.[22] The monarch clockwork has been determined to be a combination of the Drosophila and the mammalian circadian clocks. Merlin is currently manipulating clock genes in vivo to understand many unknown specifics concerning the circadian repressive mechanisms in the monarch clockwork and to comprehend how insect clocks have evolved in many different lineages.[7] Merlin received the Klingenstein-Simon Fellowship Award to support her proposal of defining clock neuronal circuits that control seasonal behavior.[23]

Expanding the genome editing toolbox in the monarch butterfly

Previously, the only in vivo targeted mutagenesis approach available in the monarch butterfly was zinc-finger nucleases (ZFNs), which involved an embryo injection strategy.[24] Merlin recognized the need of improving targeting efficiency and revolutionized the field by introducing a new class of engineered endonucleases, TALENs and the bacterial CRISPR/Cas9 system in 2016. She is currently applying this new technology to improve the efficiency of non-homologous end-joining-mediated targeting in facilitating the recovery of germline mutants. This approach is also used to develop knock-in approaches to produce precise mutations in genes of interest.[25] The new system has provided a basis for genomic engineering in other lepidopterans and non-model insects.[15]

References


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  1. 1.0 1.1 1.2 1.3 Christine Merlin's curriculum vitae
  2. 2.0 2.1 "Migrating Monarch Butterflies 'Nose' Their Way To Mexico, Neurobiologists Discover". ScienceDaily. Retrieved 2017-08-02.
  3. "Public Member Directory | SRBR: Society for Research on Biological Rhythms". srbr.org. Retrieved 2018-06-10.
  4. "Student Travel Awards – International Society of Chemical Ecology". www.chemecol.org. 2006. Retrieved 2017-04-13.
  5. "Charles A. King Trust Postdoctoral Fellowship Program Recipients" (PDF).
  6. University, The Rockefeller. "The Esther A. & and Joseph Klingenstein Fund, Inc". www.klingfund.org. Retrieved 2018-06-07.
  7. 7.0 7.1 Reppert, Steven M.; Guerra, Patrick A.; Merlin, Christine (2016-01-01). "Neurobiology of Monarch Butterfly Migration". Annual Review of Entomology. 61 (1): 25–42. doi:10.1146/annurev-ento-010814-020855. PMID 26473314.
  8. Emery, Patrick; Francis, Michael (2008-07-08). "Circadian rhythms: timing the sense of smell". Current Biology. 18 (13): R569–571. doi:10.1016/j.cub.2008.05.011. ISSN 0960-9822. PMID 18606130.
  9. 9.0 9.1 Merlin, Christine; Gegear, Robert J.; Reppert, Steven M. (2009-09-25). "Antennal Circadian Clocks Coordinate Sun Compass Orientation in Migratory Monarch Butterflies". Science. 325 (5948): 1700–1704. doi:10.1126/science.1176221. ISSN 0036-8075. PMC 2754321. PMID 19779201.
  10. College of Science Communications, Texas A&M University (14 November 2013). "LIKE CLOCKWORK: Texas A&M Biologist Says Butterfly's Epic Journey Tied to Its Antennae". Texas A&M Science. Retrieved 2017-04-13.
  11. Comish, Chris. "Texas A&M Biologist Christine Merlin Relates Monarch Butterfly's Migration To Its Antennae". BioNews Texas. Retrieved 2017-04-13.
  12. Chapman, Jason W.; Drake, V. Alistair; Reynolds, Don R. (2011-01-01). "Recent insights from radar studies of insect flight". Annual Review of Entomology. 56: 337–356. doi:10.1146/annurev-ento-120709-144820. ISSN 1545-4487. PMID 21133761.
  13. Chapman, Jason W.; Reynolds, Don R.; Wilson, Kenneth (2015-03-01). "Long-range seasonal migration in insects: mechanisms, evolutionary drivers and ecological consequences". Ecology Letters. 18 (3): 287–302. doi:10.1111/ele.12407. ISSN 1461-0248. PMID 25611117.
  14. Varga, Adrienn G.; Ritzmann, Roy E. (2016-07-25). "Cellular Basis of Head Direction and Contextual Cues in the Insect Brain". Current Biology. 26 (14): 1816–1828. doi:10.1016/j.cub.2016.05.037. ISSN 1879-0445. PMID 27397888.
  15. 15.0 15.1 Markert, Matthew J.; Zhang, Ying; Enuameh, Metewo S.; Reppert, Steven M.; Wolfe, Scot A.; Merlin, Christine (2016-04-07). "Genomic Access to Monarch Migration Using TALEN and CRISPR/Cas9-Mediated Targeted Mutagenesis". G3 (Bethesda, Md.). 6 (4): 905–915. doi:10.1534/g3.116.027029. ISSN 2160-1836. PMC 4825660. PMID 26837953.
  16. 16.0 16.1 Zhan, Shuai; Merlin, Christine; Boore, Jeffrey L.; Reppert, Steven M. (2011-11-23). "The monarch butterfly genome yields insights into long-distance migration". Cell. 147 (5): 1171–1185. doi:10.1016/j.cell.2011.09.052. ISSN 1097-4172. PMC 3225893. PMID 22118469.
  17. University of Massachusetts Medical School (28 November 2011). "Monarch butterfly genome sequenced". www.sciencedaily.com. ScienceDaily. Retrieved 2017-04-13.
  18. Cell Press (21 November 2011). "Introducing the monarch butterfly genome". www.sciencedaily.com. ScienceDaily. Retrieved 2017-04-13.
  19. Zhen, Ying; Aardema, Matthew L.; Medina, Edgar M.; Schumer, Molly; Andolfatto, Peter (2012-09-28). "Parallel Molecular Evolution in an Herbivore Community". Science. 337 (6102): 1634–1637. doi:10.1126/science.1226630. ISSN 0036-8075. PMC 3770729. PMID 23019645.
  20. Kawahara, Akito Y.; Breinholt, Jesse W. (2014-08-07). "Phylogenomics provides strong evidence for relationships of butterflies and moths". Proc. R. Soc. B. 281 (1788): 20140970. doi:10.1098/rspb.2014.0970. ISSN 0962-8452. PMC 4083801. PMID 24966318.
  21. Gurumurthy, Channabasavaiah B.; Grati, M'hamed; Ohtsuka, Masato; Schilit, Samantha L. P.; Quadros, Rolen M.; Liu, Xue Zhong (September 2016). "CRISPR: a versatile tool for both forward and reverse genetics research". Human Genetics. 135 (9): 971–976. doi:10.1007/s00439-016-1704-4. ISSN 1432-1203. PMC 5002245. PMID 27384229.
  22. Johnson, Carl Hirschie (2010-10-01). "Circadian clocks and cell division". Cell Cycle. 9 (19): 3864–3873. doi:10.4161/cc.9.19.13205. ISSN 1538-4101. PMC 3047750. PMID 20890114.
  23. University, College of Science Communications, Texas A&M (20050526). "Texas A&M Biologist Christine Merlin Honored as Klingenstein-Simons Neuroscience Fellow". Texas A&M Science. Retrieved 2018-06-07. Check date values in: |date= (help)
  24. Lloyd, Alan; Plaisier, Christopher L.; Carroll, Dana; Drews, Gary N. (2005-02-08). "Targeted mutagenesis using zinc-finger nucleases in Arabidopsis". Proceedings of the National Academy of Sciences of the United States of America. 102 (6): 2232–2237. doi:10.1073/pnas.0409339102. ISSN 0027-8424. PMID 15677315.
  25. CHEN, Lei; WANG, Gui; ZHU, Ya-Nan; XIANG, Hui; WANG, Wen (2016-07-18). "Advances and perspectives in the application of CRISPR/Cas9 in insects". Zoological Research. 37 (4): 136–143. doi:10.13918/j.issn.2095-8137.2016.4.220. ISSN 2095-8137. PMC 4978943. PMID 27469253.