Christine Merlin

Last updated

Christine Merlin is a French chronobiologist and an associate professor of biology at Texas A&M University. [1] Merlin's research focuses on the underlying genetics of the monarch butterfly circadian clock and explores how circadian rhythms modulate monarch behavior and navigation. [2]

Contents

Christine Merlin
ChristineMerlin.jpg
BornSeptember 24, 1980
Hautes-Pyrénées, France
NationalityFrench
Alma mater Pierre and Marie Curie University
Known forSun compass navigation in migratory monarch butterflies
Scientific career
Fields Chronobiology, genetics, entomology
Institutions Texas A&M University
University of Massachusetts Medical School
Pierre and Marie Curie University
Website https://www.merlinlab.org/

Background

Merlin was born on September 24, 1980, in southwestern France. She attended Pierre and Marie Curie University in Paris, where she received a BS in animal biology, an MS in invertebrate physiology, and finally her PhD in insect physiology in 2006. [1] She studied circadian rhythms in moths in Versailles at the National Institute for Research on Agronomy in the lab of Emmanuelle Jacquin-Joly and Martine Maibeche-Coisne while studying for her doctorate. In 2007, she began working in the lab of Steven Reppert at the University of Massachusetts Medical School. There, she studied the migration of monarch butterflies, established reverse genetics in this new model system, and collaborated on a paper outlining the monarch genome. [1] [3] [4]

In 2013, she became an assistant professor of biology at Texas A&M University, where she works now. She joined the Center of Biological Clocks Research as a faculty member studying biology, specifically the circadian clock regulation of monarch butterfly migration. She also became a faculty member of Texas A&M's Genetics and Neuroscience interdisciplinary program in 2014, as well as their Ecology and Evolutionary Biology interdisciplinary program in 2015. [1] [3]

Scientific contributions

Merlin has helped publish over 25 papers during the course of her career and has garnered over 2000 citations for her work. [5]

The migration of monarch butterflies and its control by circadian clocks

Monarch butterflies use the sun as a compass to precisely orient themselves across long distances during migration. [6] [7] Merlin and colleagues determined that circadian clocks located in the antennae play a significant role in navigation in migratory monarch butterflies. [8] Using tests of necessity, Merlin and colleagues analyzed migratory butterfly orientation with intact antennae, without antennae, or with antennae coated with black paint, and concluded that butterflies without antennae or with antennae harboring desynchronized antennal clocks (coated black) were unable to orient relative to the sun. [9] She isolated butterfly antennae in vitro and discovered that they sustained 24-hour rhythms in constant conditions after entrainment to light-dark cycles. By measuring expression of clock genes Per, Tim, and Cry2, Merlin determined that a circadian clock exists in the monarch antennae, functioning independently of the brain clock. [7] [8]

Monarch butterflies use a time-compensated sun compass that is a part of the insect's light-entrained circadian clocks located in the antennae. [8]  Merlin and colleagues conducted a test of sufficiency to determine if one or both antennae are needed to properly orient. They found that either antenna can be sufficient for time compensation, but surprisingly that butterflies with one of their antennae painted black and the other painted clear had disoriented flight. [7] [10]  In this experimental condition, the antenna painted black would block entrainment from light cues while the antenna painted clear would allow entrainment from light cues. When the black-painted antenna from this experimental condition was ablated, the butterfly would then be able to properly orient by using just the single clear-painted antenna to entrain. [7]  The team also observed that Per and Tim gene expression was highly rhythmic in the clear-painted antennae, but disrupted in the black-painted antennae. [10]  Merlin and coworkers concluded that each antenna has its own clock outputs that are then processed together in the sun compass to direct the orientation of flight.

In 2011, Merlin (along with Steven Reppert, Shuai Zhan, and Jeffrey Boore) contributed to outlining the genome of the migratory monarch butterfly and described the operation of circadian clocks as a method of regulating migration. The monarch clock relies on a transcription-translation feedback loop (TTFL) that contains many of the same genetic components as the clocks of other arthropods, such as Drosophila melanogaster . [11] One notable difference between the monarch clock and the Drosophila melanogaster clock is the appearance of both a light-sensitive CRY1 and a transcriptionally repressive CRY2 in the monarch clock, while Drosophila melanogaster only contains CRY1. [12] [13] As most arthropods have both CRY types, this result provided additional evidence that both CRY were at “the base of arthropod evolution.” They highlighted two main uses for the clock. One use is for sun compass orientation, which allows the monarch to navigate towards its destination by detecting the horizontal position of the sun and the polarized skylight patterns produced. The other use is for the initiation of migration by detecting decreasing day length in the autumn. [12]

Genetic editing: TALENs & CRISPR/Cas9

Merlin and her lab have been consistently interested in exploring methods of selective genetic editing via tools such as zinc finger proteins, which enable the creation of targeted gene knockouts within a specified locus. In 2016, Merlin and colleagues demonstrated that both TALENs and CRISPR/Cas9 technologies could be utilized in a similar manner to create highly efficient, heritable, targeted mutagenesis at selected genomic loci. [14] Merlin and her team were able to generate genetic knockouts of the Cry2 and Clk genes within the monarch genome, two notable clock genes responsible in part for the regulation and modulation of the monarch circadian clock. These knockouts were shown to be heritable, with the injection of less than 100 eggs being sufficient to recover mutant progeny; enabling the generation of mutant knockout lines in around 3 months. [14] These findings provided new research methods for the genetic manipulation and study of monarch clock genes, as is currently being explored by the Merlin Lab.

Monarch migration, photoperiodic induction and genetics

While researching monarchs, Merlin headed a paper alongside graduate students Samantha E. Liams and Aldrin B. Lugena and delved into a deeper understanding of monarch migration, its concomitant photoperiodic induction of diapause, and the underlying genetic components. [15] [16] Monarchs who migrate in the fall experience a reproductive diapause response to prepare for their migration, which is triggered by the shortened days and colder temperatures of autumn. [7] In laboratory conditions, female monarchs produce less mature oocytes in short photoperiods than in long ones, and Merlin and colleagues genetically demonstrated the involvement of clock genes in the response. They also identified the vitamin A pathway in the brain as being differentially regulated in a photoperiod manner. [15] Using a CRISPR/Cas9-mediated loss of function mutant of gene nina B1, a gene that encodes the rate limiting enzyme that converts β-carotene into retinal, they demonstrated the necessity of this pathway for the photoperiodic induction of reproductive diapause. As in other insects, diapause in monarchs is known to result from juvenile hormone deficiency in the corpora cardiaca-corpora allata complex, but the link between the hormone and vitamin A is currently unknown. [15]

Magnetoreception

In 2021, Merlin was credited as assisting in a research article focused on the magnetoreception of monarch butterflies. [17] While the molecular and cellular mechanisms underlying magnetic sensing has not yet been discovered, the connection to the photoexcitation of CRY proteins has been linked to both CRY1 in Drosophila and CRY2 in monarchs and humans. [7] This discovery in humans and monarchs was identified due to the finding that overexpression in CRY-deficient flies restored magnetosensitivity, suggesting they perform photochemical reactions for the magnetosensitivity in the fly's cellular environment. [17] In order to test reorientation using magnetic inclination in monarchs, both fall migrant monarchs and wild-type laboratory monarchs were placed in a flight simulator that manipulated different magnetic field parameters: declination, inclination, and intensity. It was found that both variants of monarchs did not display hyperactivity to the geomagnetic field, but both variants did display an increase in wingbeats upon reversing magnetic inclination. Creating a behavioral assay from this experiment led to the evaluation that the Drosophila CRY1 (dpCry1) was necessary for monarch light-dependent magnetoreception, while the Drosophila CRY2 (dpCry2) was not. [17] The antennae and compound eyes were tested to see if they were necessary for light-dependent magnetoreception. Blocking either one of these organs with black paint led to impaired responses to ambient magnetic inclination and reversal of ambient magnetic inclination. This indicates that the monarch's antennae and compound eyes are necessary for magnetosensing, and that impairing one of these organs cannot be compensated by the other. [17]

Ongoing research

As of 2021, the Merlin lab is currently focused on utilizing reverse genetic tools to further unravel clockwork mechanisms in the monarch, determine how previously identified candidate genes contribute to butterfly migration and photoperiodic sensing, as well as dissect the genetic basis of the magnetic sense. [2] The lab is currently working with known clock genes in vivo to understand circadian repressive mechanisms within the monarch and gain further knowledge regarding how insect clocks have evolved. Merlin is also exploring means to expand the monarch genetic toolbox with a focus on developing a reliable CRISPR/Cas9-mediated knock-in approach to introduce reporter tags into loci of interest within the monarch genome and gain insights into the clock circuitry in the brain. [2]

Timeline of selected publications

Honors and awards

The Merlin Lab receives funding from the National Science Foundation, the National Institutes of Health, and the Esther A. & Joseph Klingenstein Fund. [2] Merlin has received the following awards for her work in circadian biology:

See also

Related Research Articles

<span class="mw-page-title-main">Suprachiasmatic nucleus</span> Part of the brains hypothalamus

The suprachiasmatic nucleus or nuclei (SCN) is a small region of the brain in the hypothalamus, situated directly above the optic chiasm. The SCN is the principal circadian pacemaker in mammals, responsible for generating circadian rhythms. Reception of light inputs from photosensitive retinal ganglion cells allow the SCN to coordinate the subordinate cellular clocks of the body and entrain to the environment. The neuronal and hormonal activities it generates regulate many different body functions in an approximately 24-hour cycle.

A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase and is synchronized with solar time.

<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.

Period (per) is a gene located on the X chromosome of Drosophila melanogaster. Oscillations in levels of both per transcript and its corresponding protein PER have a period of approximately 24 hours and together play a central role in the molecular mechanism of the Drosophila biological clock driving circadian rhythms in eclosion and locomotor activity. Mutations in the per gene can shorten (perS), lengthen (perL), and even abolish (per0) the period of the circadian rhythm.

<span class="mw-page-title-main">PER2</span> Protein-coding gene in the species Homo sapiens

PER2 is a protein in mammals encoded by the PER2 gene. PER2 is noted for its major role in circadian rhythms.

<span class="mw-page-title-main">FBXL3</span> Protein-coding gene in the species Homo sapiens

FBXL3 is a gene in humans and mice that encodes the F-box/LRR-repeat protein 3 (FBXL3). FBXL3 is a member of the F-box protein family, which constitutes one of the four subunits in the SCF ubiquitin ligase complex.

<span class="mw-page-title-main">ARNTL2</span> Protein-coding gene in humans

Aryl hydrocarbon receptor nuclear translocator-like 2, also known as Arntl2, Mop9, Bmal2, or Clif, is a gene.

An Error has occurred retrieving Wikidata item for infobox Period circadian protein homolog 1 is a protein in humans that is encoded by the PER1 gene.

<span class="mw-page-title-main">Basic helix-loop-helix ARNT-like protein 1</span> Protein-coding gene in the species Homo sapiens

Basic helix-loop-helix ARNT-like protein 1 or aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL), or brain and muscle ARNT-like 1 is a protein that in humans is encoded by the BMAL1 gene on chromosome 11, region p15.3. It's also known as MOP3, and, less commonly, bHLHe5, BMAL, BMAL1C, JAP3, PASD3, and TIC.

<span class="mw-page-title-main">PAS domain</span> Protein domain

A Per-Arnt-Sim (PAS) domain is a protein domain found in all kingdoms of life. Generally, the PAS domain acts as a molecular sensor, whereby small molecules and other proteins associate via binding of the PAS domain. Due to this sensing capability, the PAS domain has been shown as the key structural motif involved in protein-protein interactions of the circadian clock, and it is also a common motif found in signaling proteins, where it functions as a signaling sensor.

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.

Steven M. Reppert is an American neuroscientist known for his contributions to the fields of chronobiology and neuroethology. His research has focused primarily on the physiological, cellular, and molecular basis of circadian rhythms in mammals and more recently on the navigational mechanisms of migratory monarch butterflies. He was the Higgins Family Professor of Neuroscience at the University of Massachusetts Medical School from 2001 to 2017, and from 2001 to 2013 was the founding chair of the Department of Neurobiology. Reppert stepped down as chair in 2014. He is currently distinguished professor emeritus of neurobiology.

<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">Monarch butterfly migration</span> Migrations, mainly across North America

Monarch butterfly migration is the phenomenon, mainly across North America, where the subspecies Danaus plexippus plexippus migrates each summer and autumn to and from overwintering sites on the West Coast of California or mountainous sites in Central Mexico. Other subspecies perform minor migrations or none at all. This massive movement of butterflies has been called "one of the most spectacular natural phenomena in the world".

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.

Paul Hardin is an American scientist in the field of chronobiology and a pioneering researcher in the understanding of circadian clocks in flies and mammals. Hardin currently serves as a distinguished professor in the biology department at Texas A&M University. He is best known for his discovery of circadian oscillations in the mRNA of the clock gene Period (per), the importance of the E-Box in per activation, the interlocked feedback loops that control rhythms in activator gene transcription, and the circadian regulation of olfaction in Drosophila melanogaster. Born in a suburb of Chicago, Matteson, Illinois, Hardin currently resides in College Station, Texas, with his wife and three children.

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.

Biological tests of necessity and sufficiency refer to experimental methods and techniques that seek to test or provide evidence for specific kinds of causal relationships in biological systems. A necessary cause is one without which it would be impossible for an effect to occur, while a sufficient cause is one whose presence guarantees the occurrence of an effect. These concepts are largely based on but distinct from ideas of necessity and sufficiency in logic.

Raleighplots, or Rayleigh plots, are statistical graphics that serve as graphical representations for a Raleigh test that map a mean vector to a circular plot. Raleigh plots have many applications in the field of chronobiology, such as in studying butterfly migration patterns or protein and gene expression, and in other fields such as geology, cognitive psychology, and physics.

Charles J. Weitz is a chronobiologist and neurobiologist whose work primarily focuses on studying the molecular biology and genetics of circadian clocks.

References

  1. 1 2 3 4 Daugherty, McKensie. "Faculty Page: Christine Merlin". Texas A&M Biology. Retrieved 2021-05-05.
  2. 1 2 3 4 "Research". merlin-lab. Retrieved 2021-04-22.
  3. 1 2 3 4 "Christine Merlin CV" (PDF). Archived (PDF) from the original on 2021-04-22.
  4. ↑ Merlin, Christine; Beaver, Lauren E.; Taylor, Orley R.; Wolfe, Scot A.; Reppert, Steven M. (2013-01-01). "Efficient targeted mutagenesis in the monarch butterfly using zinc-finger nucleases". Genome Research. 23 (1): 159–168. doi:10.1101/gr.145599.112. ISSN   1088-9051. PMC   3530676 . PMID   23009861.
  5. ↑ "Christine Merlin". scholar.google.com. Retrieved 2021-04-21.
  6. ↑ Pennisi, Elizabeth (2019-12-18). "Mysterious monarch migrations may be triggered by the angle of the Sun". Science | AAAS. Retrieved 2021-05-06.
  7. 1 2 3 4 5 6 Reppert, Steven M.; de Roode, Jacobus C. (2018-09-10). "Demystifying Monarch Butterfly Migration". Current Biology. 28 (17): R1009–R1022. doi: 10.1016/j.cub.2018.02.067 . ISSN   1879-0445. PMID   30205052.
  8. 1 2 3 4 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. Bibcode:2009Sci...325.1700M. doi:10.1126/science.1176221. ISSN   0036-8075. PMC   2754321 . PMID   19779201.
  9. ↑ Buchen, Lizzie (2009-09-24). "Butterflies' migrational timekeeper found". Nature.
  10. 1 2 Guerra, Patrick A.; Merlin, Christine; Gegear, Robert J.; Reppert, Steven M. (2012-07-17). "Discordant timing between antennae disrupts sun compass orientation in migratory monarch butterflies". Nature Communications. 3 (1): 958. Bibcode:2012NatCo...3..958G. doi:10.1038/ncomms1965. ISSN   2041-1723. PMC   3962218 . PMID   22805565.
  11. ↑ Allada, Ravi; Chung, Brian Y. (2010-03-17). "Circadian Organization of Behavior and Physiology in Drosophila". Annual Review of Physiology. 72 (1): 605–624. doi:10.1146/annurev-physiol-021909-135815. ISSN   0066-4278. PMC   2887282 . PMID   20148690.
  12. 1 2 3 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   0092-8674. PMC   3225893 . PMID   22118469.
  13. ↑ Zhu, Haisun; Sauman, Ivo; Yuan, Quan; Casselman, Amy; Emery-Le, Myai; Emery, Patrick; Reppert, Steven M. (2008-01-08). "Cryptochromes Define a Novel Circadian Clock Mechanism in Monarch Butterflies That May Underlie Sun Compass Navigation". PLOS Biology. 6 (1): e4. doi:10.1371/journal.pbio.0060004. ISSN   1545-7885. PMC   2174970 . PMID   18184036.
  14. 1 2 3 Markert, Matthew J; Zhang, Ying; Enuameh, Metewo S; Reppert, Steven M; Wolfe, Scot A; Merlin, Christine (2016-04-01). "Genomic Access to Monarch Migration Using TALEN and CRISPR/Cas9-Mediated Targeted Mutagenesis". G3: Genes, Genomes, Genetics. 6 (4): 905–915. doi:10.1534/g3.116.027029. ISSN   2160-1836. PMC   4825660 . PMID   26837953.
  15. 1 2 3 Merlin, Christine; Iiams, Samantha E.; Lugena, Aldrin B. (2020-09-01). "Monarch Butterfly Migration Moving into the Genetic Era". Trends in Genetics. 36 (9): 689–701. doi: 10.1016/j.tig.2020.06.011 . ISSN   0168-9525. PMID   32713598.
  16. ↑ Zhan, Shuai; Zhang, Wei; Niitepõld, Kristjan; Hsu, Jeremy; Haeger, Juan Fernández; Zalucki, Myron P.; Altizer, Sonia; de Roode, Jacobus C.; Reppert, Steven M.; Kronforst, Marcus R. (2014-10-16). "The genetics of monarch butterfly migration and warning coloration". Nature. 514 (7522): 317–321. Bibcode:2014Natur.514..317Z. doi:10.1038/nature13812. ISSN   0028-0836. PMC   4331202 . PMID   25274300.
  17. 1 2 3 4 5 Wan, Guijun; Hayden, Ashley N.; Iiams, Samantha E.; Merlin, Christine (2021-02-03). "Cryptochrome 1 mediates light-dependent inclination magnetosensing in monarch butterflies". Nature Communications. 12 (1): 771. Bibcode:2021NatCo..12..771W. doi:10.1038/s41467-021-21002-z. ISSN   2041-1723. PMC   7859408 . PMID   33536422.
  18. ↑ Jacquin-Joly, Emmanuelle; Merlin, Christine (2004-12-01). "Insect olfactory receptors: contributions of molecular biology to chemical ecology". Journal of Chemical Ecology. 30 (12): 2359–2397. doi:10.1007/s10886-004-7941-3. ISSN   0098-0331. PMID   15724962. S2CID   25060812.
  19. ↑ Reppert, Steven M.; Guerra, Patrick A.; Merlin, Christine (2016-03-16). "Neurobiology of Monarch Butterfly Migration". Annual Review of Entomology. 61: 25–42. doi: 10.1146/annurev-ento-010814-020855 . PMID   26473314.
  20. ↑ Lugena, Aldrin B.; Zhang, Ying; Menet, Jerome S.; Merlin, Christine (2019-07-23). Kramer, Achim (ed.). "Genome-wide discovery of the daily transcriptome, DNA regulatory elements and transcription factor occupancy in the monarch butterfly brain". PLOS Genetics. 15 (7): e1008265. doi:10.1371/journal.pgen.1008265. ISSN   1553-7404. PMC   6677324 . PMID   31335862.
  21. ↑ "Texas A&M Biologist Christine Merlin Honored as Klingenstein-Simons Neuroscience Fellow". Texas A&M College of Science. 2017-09-07. Retrieved 2021-04-22.
  22. ↑ "Two Texas A&M Science Faculty Named 2020 Presidential Impact Fellows". Texas A&M College of Science. 2020-11-13. Retrieved 2021-04-22.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.