Presented annually as a joint project of the Esther A. and Joseph Klingenstein Fund and the Simons Foundation, the Klingenstein-Simons Fellowship Awards are intended to support early career investigators engaged in basic or clinical research that may lead to a better understanding of neurological and psychiatric disorders. Viewed as among the nation’s oldest and most illustrious fellowships for young investigators engaged in groundbreaking neuroscience research, the coveted awards are aimed at advancing cutting-edge investigations by promoting higher-risk, potentially higher-reward projects at a critical career stage when funding can be a challenge.
Merlin’s three-year, $225,000 award will support her proposal, “Defining clock neuronal circuits that control seasonal behavior,” and her ongoing research to better understand the genetic and neuronal bases behind Monarch butterfly migration — a fascinating and arduous journey she believes is tied to circadian clocks within the insect’s antennae.
Merlin’s lab within the Texas A&M Center for Biological Clocks Research (CBCR) uses Monarchs as a model to study animal migration, the role of circadian clocks in regulating daily and seasonal animal physiology and behavior, and the evolution of the animal clockwork. The majestic Monarch offers unique opportunities to provide mechanistic insights into these questions, given that Monarchs annually perform one of the most impressive long-distance migrations, relying on their circadian clock for navigation.
“Christine not only complements our already strong group researching various aspects of biological rhythms, but she also helps broaden our department by bringing in a new model system she pioneered as a postdoc in Steve Reppert’s lab in the Neurobiology Department at the University of Massachusetts Medical School,” said Dr. Thomas D. McKnight, professor and head of the Texas A&M Department of Biology. “Several of the reference letters supporting her 2013 application for our faculty position pointed out that she is destined to become a star. I supposed much of that was the typical hyperbole that sometimes shows up in those letters, but given her dedication, passion, technical adroitness, and the charismatic Monarch butterfly system she has developed, I have rapidly become a believer.”
Although the molecular mechanisms of biological clocks are well understood and likely exist in almost all organisms on earth, those mechanisms as well as our understanding of them remains limited to a few species, primarily fruit flies, whose clock has some distinct differences from those of mammals. Because clock components in butterflies are more similar to mammalian clocks, researchers like Merlin are eager to explore the broader evolutionary implications using novel genomic and reverse-genetic approaches to identify candidate genes and test their functions.
“Christine is one of 12 circadian biologists within the campus-wide Center for Biological Clocks Research at Texas A&M, which not only provides broad expertise and training opportunities for students, but also supports and facilitates collaboration among its faculty,” McKnight added. “Her extensive experience and technical expertise allow her to interact with a broad variety of researchers across our campus, and she is working with some of them to develop transgenic approaches for their non-model organisms.”
One specific approach, CRISPR-Cas9, was adapted from a bacterial mechanism used to recognize and destroy invading viruses. This gene-editing technology can be used to alter the expression or function of virtually any target gene, including those involved in clock function. Merlin and other molecular biologists have pioneered its use to open up the study of animals like butterflies that were once off limits to other molecular genetic approaches. Using CRISPR-Cas9 technology, scientists can edit a genome by cutting it at specific sites and letting the natural DNA repair process introduce mutations. They can thus knock out specific genes involved in circadian function, thereby harnessing natural pathways to change the DNA of organisms experimentally in their efforts to learn the role of specific gene products.
Thus far in her research, Merlin has succeeded in altering key biological clock-related genes in the Monarch and now is studying how that affects these new strains of butterflies, from their responses to environmental cues to their migration. Much of her work continues to refine the targeted mutagenesis approaches she has developed to further investigate the neural network that links the peripheral circadian clock in Monarch antennae to the sun compass in the brain.
In addition to being one of only four authors on the groundbreaking 2011 Cell paper describing the complete genome of Monarchs, Merlin is one of three authors of the highly cited review on the neurobiology of Monarch migration published in Annual Reviews of Entomology. She served as one of the plenary speakers at the April 2017 Genetics of Migration Symposium in Germany and is participating in the nationwide National Science Foundation Insect Genetic Technologies Network.
“Even at this early stage of her career, Christine’s work is receiving wide recognition,” McKnight said. “Several people from other institutions have mentioned how lucky we are to have such a talented young researcher in our department. She is already making valuable and highly visible contributions to her field, and she is well on her way to prominence.”
In mid-August, Merlin’s lab also received funding as part of a National Institutes of Health National Institute of General Medical Sciences RO1 [research project grant] award to investigate mechanisms of circadian repression in collaboration with the lab of fellow Texas A&M biologist and CBCR Director Paul Hardin.
“Christine’s Klingenstein-Simons Neuroscience Fellowship studies will revolutionize behavioral neuroscience research by developing critical genetic tools for mapping circadian clock neuronal circuits that control seasonal migration,” Hardin said. “Such tools are essential for determining if clock neuronal circuits physically change with migration status over the year and also will facilitate the analysis of molecular mechanisms that drive these seasonal changes. Importantly, applying CRISPR-Cas9 technology to generate tools for mapping neuronal circuits can be extended to other non-model insects and the development of other types of neuronal activation and silencing tools that can be used to probe circuit function. The potential for these studies is immense, and I have every confidence that Christine will exceed all expectations.”
To see the complete list of 2017 Klingenstein-Simons Neuroscience Fellows or learn more about the program, visit http://www.klingfund.org/fellows/fellows17.php.
For additional information Merlin and her research, go to http://www.merlinlab.org.
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Contact: Shana K. Hutchins, (979) 862-1237 or firstname.lastname@example.org or Dr. Christine Merlin, (979) 862-2457 or email@example.com