Nilay Yapici

Nilay Yapici (born c. 1981) is a Turkish neuroscientist and the Nancy and Peter Meinig Family Investigator in the Life Sciences and Adelson Sesquicentennial Fellow in the Department of Neurobiology and Behavior at Cornell University in Ithaca, New York. Yapici studies the neural circuits underlying decision making and feeding behavior in fruit fly models to pave the way towards an understanding of how to target and treat obesity and eating disorders in patients.

Nilay Yapici
Bornc. 1981 (age 38–39)
Samsun, Turkey
NationalityTurkish
Alma materBogazici University, Institute of Molecular Pathology at the University of Vienna
Known forDiscovery of Sex Peptide Receptor and Ingestion Neurons in fruit flies
Scientific career
FieldsNeuroscience
InstitutionsCornell University

Early life and education

Yapici was born in Samsun, Turkey in 1981.[1] She attended Bogazici University, in Istanbul, Turkey to pursue her undergraduate studies in molecular biology and genetics.[2] During her undergraduate degree, Yapici explored various research opportunities both at her institution and abroad. In 2002, Yapici was a summer Visiting Student in the lab of Mark Gluck at Rutgers University in New Jersey where she studied the cognitive neuroscience of learning and memory.[3] The following summer, Yapici again conducted research abroad, this time in Switzerland at the Zurich University Hospital Department of Pathology in the lab of Adriano Aguzzi studying prion diseases.[4] Back at Bogazici University in 2003, Yapici began working in the lab of Kuyas Bugra, where she completed her honors thesis exploring signalling mechanisms in retinal tissue.[5]

After graduating with her B.Sc. in 2004, Yapici pursued her graduate training in Molecular Biology within the Institute of Molecular Pathology at the University of Vienna, Austria.[6] Yapici was mentored by Barry Dickson during her PhD, where she explored the genetic basis of complex innate behavior in drosophila.[1] During this time, Yapici helped to discover the receptor for sex peptide.[7]

In 2009, Yapici completed her graduate training and then moved to America to conduct her postdoctoral studies in the lab of Leslie Vosshall at the Rockefeller University in New York City.[2] Her research in the Vosshall lab continued to use drosophila as a model organism, however she began to explore the neural circuits governing feeding behavior.[7] Yapici developed a method in the lab to measure drosophila food intake with high resolution.[7] Yapici completed her postdoctoral work in 2016 before starting her own lab at Cornell University.[6]

Discovery of sex peptide receptor in drosophila

During graduate school, Yapici explored the underlying genetic mechanisms of post-mating behavioral responses of female flies to understand, at a fundamental level, how an environmental influence can lead to a change in physiology and behavior. To answer her questions, Yapici and her colleagues developed a high throughout egg laying assay such that they could observe receptivity and egg-laying behavior in virgin versus recently mated females.[8] This allowed them to probe the genetic differences between a receptive female and a post-mated non-receptive female to understand what was leading to this change in mating behavior after copulation.[9] Using an inducible RNAi library technique to genetically screen the female drosophila, they found many genes involved in egg-laying and mating behaviors and the genes that markedly stood out were the gene for Sex Peptide and the gene for Sex Peptide Receptor.[8] Yapici and her colleagues were the first to characterize the Sex Peptide Receptor (SPR), which is a G-coupled protein receptor expressed in the brain and ventral nerve chord as well as the female reproductive tract.[8] They found through knockout studies that SRP is critical to the post-mating behavioral change, and without SPR, post-mated females continue to express behavioral phenotypes of virgins.[8] Two other important genes that came out of their studies were TBh, important in octopamine synthesis, and VMAT, important in octopamine transport.[9] They found that knockdown of these genes lead to similar behavioral phenotypes as flies lacking SRP.[9]  By identifying the receptor critical for modulating female reproductive behaviors, Yapici’s work helped to open possibilities for control of pests by targeting this genetic driver of reproductive behaviors.[9]

Since SPR is also expressed in the cells of organisms who do not have exposure to SP as drosophila do, Yapici and her team explored alternative ligands for SPR and found myoinhibitory peptides (MIPs) to be another type of SPR ligand and they appeared to be conserved across a spectrum of invertebrates.[10] Interestingly, MIPs are not derived from male sex organs as SP is, and MIPs are not necessary to promote the switch in behavior post-mating in females, while SP is necessary.[10]

Following this work, Yapici and her colleagues decided to patent the idea of targeting the SPR as a method of insect control.[11] They proposed administration of an analogue of SP to females which will bind to SPR and cause the shift in behavior from that of a virgin to that of a post-mated female without the need for copulation.[11] This could prevent copulation, and thus also egg laying and blood sucking in insects like mosquitoes who only suck blood after laying eggs.[11]

Career and research

In 2016, Yapici was recruited to Cornell University to become the Nancy and Peter Meinig Family Investigator in the Life Sciences and Adelson Sesquicentennial Fellow in the Department of Neurobiology and Behavior.[2] Yapici’s lab studies how behavioral states regulate neural circuitry and drive motvational behaviors using fly models.[12] Yapici is addressing this question using hunger and feeding as a model system to probe how environmental cues prompt decision making and drive motivation signals to eat or not to eat in fruit flies.[12] They use a multitude of advanced technologies to probe neural circuitry, genetics, and behavior in flies.[12]

At Cornell University, Yapici is a part of the new National Science Foundation funded NeuroNex Hub.[13] Yapici, along with four other engineers and scientists at Cornell, have been tasked with developing innovative methods to image the brain at in less time, greater depth, and at greater volumes.[13] The interdisciplinary team plans to develop tools, test them in several model organisms and then disseminate them to the Cornell community and abroad to increase the ability of scientists to probe questions about the how structure and function give rise to behavior and disease.[13]  As such, Yapici has use the recent development, a multiphoton microscope, to record neural activity in the fly brain in response to olfactory cues.[14] They were able to use a non-invasive approach to maintain functional and structural integrity of the fly brain while imaging with two and three photon resolution to observe calcium signals in mushroom body Kenyon cells in response to odours.[14] Next, Yapici will use this tool to better understand how hunger is encoded in the fly brain.[13]

Feeding behavior in drosophila

During her postdoctoral work in the Vosshall Lab, Yapici began to explore feeding behavior in drosophila. Not only did she elucidate a novel neural circuit regulating ingestion, but she also developed a novel method to analyze fly food consumption in real-time at high resolution.[15] Since observing fly consumption is extremely difficult at individual fly resolution, many groups have explored ways to directly measure ingestion, but most required manual measurements.[15] Yapici set to improve upon this technology and created “Expresso”, a novel and innovative tool to study temporal dynamics of food ingestion in flies in an automated manner.[15] Her technology had multiple single-fly feeding chambers, each with a sensor that enabled detection of liquid (food) levels in real time.[15] With this innovative technology, Yapici was able to detect temporally precise ingestion, related to hunger state, and further identify 12 cholinergic local interneurons that she called Ingestion Neurons (IN1) that were necessary for this behavior.[15] Since IN1 neurons receive pre-synaptic inputs from pharyngeal neurons, she hypothesized that IN1 neurons detect and monitor ingestion such that after subsequent feeding bouts, the activity of these neurons proportionally decreased, as an indicator of feeding or hunger state.[15] Further using optogenetics, they were able to causally test the implications of this circuit in feeding and found that stimulation increased the level of consumption in flies.[15]

After starting her lab at Cornell, Yapici started to examine, in fine detail, the expression of various Ionotropic receptors involved in taste function in flies.[16] A large propotion of gustatory perception is mediated by Gustatory Receptors, but another large component of taste perception is mediated by Ionotropic receptors which are ligand gated ion channels.[16] They surveyed many receptors in the ionotropic family associated with gustatory perception and they found one that mediated perception of carbonation and drove both physiological and behavioral responses.[16] They also showed that this same receptor is necessary for sugar-sensing through Gustatory Receptors indicating the extent of combinatorial coding that exists in fruit fly gustatory perception.[16] In a follow up paper, Yapici and her team found that IR56d, a type of Ionotropic Receptor implicated in gustation, was essential for physiological responses to carbonation and fatty acids but not sugars.[17] Further, through IR56d, carbonation is a behavioral attractant for flies.[17] Elucidating how specific sensory processes guide behavior in simple organisms will enlighten how these processes work in higher level organisms in the future of neuroscience.[17]

Awards and honors
  • 2019 National Institutes of Health’s Institute of General Medical Sciences Grant[18]
  • 2018 Glenn Foundation for Medical Research and American Federation for Aging Research Grants for Early Career Investigators[19]
  • 2017 NSF NeuroNex Neurotechnology Hub Awards[20]
  • 2017 Pew Biomedical Scholar[21]
  • 2017 Alfred P. Sloan Foundation[22]
  • 2009 EMBO Long Term Fellowship[7]
  • 2009 Human Frontiers (HFSP) Long Term Fellowship[7]
  • Lindau Nobel Laureate Meeting (Selected Participant)[7]

Select publications
  • Sanchez-Alcaniz JA, Silbering AF, Croset V, Zappia G, Sivasubramaniam AK, Abuin L, Sahai SY, Münch D, Steck K, Auer TO, Cruchet S, Neagu-Maier L,  Sprecher SG, Ribeiro C, Yapici N, Benton R (2018). An expression atlas of variant ionotropic glutamate receptors identifies a molecular basis of carbonation sensing. Nature communications, 9(1), 4252.[16]
  • Yapici, N., Cohn, R., Schusterreiter, C., Ruta, V., & Vosshall, L. B. (2016). A taste circuit that regulates ingestion by integrating food and hunger signals. Cell, 165(3), 715-729. [15]
  • Yapici, N., Zimmer, M., & Domingos, A. I. (2014). Cellular and molecular basis of decision‐making. EMBO Reports, 15, 1023-1035.[23]
  • Bussell, J. J., Yapici, N., Zhang, S. X., Dickson, B. J., & Vosshall, L. B. (2014). Abdominal-B neurons control Drosophila virgin female receptivity. Current Biology, 24, 1584-1595.[24]
  • Kim, Y. J., Bartalska, K., Audsley, N., Yamanaka, N., Yapici, N., Lee, J. Y. & Dickson, B. J. (2010). MIPs are ancestral ligands for the sex peptide receptor. Proceedings of the National Academy of Sciences U.S.A., 107, 6520-6525.[25]
  • Häsemeyer, M., Yapici, N., Heberlein, U., & Dickson, B. J. (2009). Sensory neurons in the Drosophila genital tract regulate female reproductive behavior. Neuron, 61, 511-518.[26]
  • Yapici, N., Kim, Y. J., Ribeiro, C., & Dickson, B. J. (2007). A receptor that mediates the post-mating switch in Drosophila reproductive behavior. Nature, 451, 33-37.[8]

References
  1. "Sabri Ülker Symposium". www.sabriulkersymposium.org. Retrieved 2020-04-29.
  2. "Neurobiologist Nilay Yapici named Pew scholar". as.cornell.edu. Retrieved 2020-04-29.
  3. "Gluck Lab Online". www.gluck.edu. Retrieved 2020-04-29.
  4. "Prof. Dr. Adriano Aguzzi". www.rna.uzh.ch. Retrieved 2020-04-29.
  5. "Retina Lab". www.retina.bio.boun.edu.tr. Retrieved 2020-04-29.
  6. "Nilay Yapici | Cornell University College of Arts and Sciences Cornell Arts & Sciences". as.cornell.edu. Retrieved 2020-04-29.
  7. "Lab Alumni". Research. Retrieved 2020-04-29.
  8. Yapici, Nilay; Kim, Young-Joon; Ribeiro, Carlos; Dickson, Barry J. (January 2008). "A receptor that mediates the post-mating switch in Drosophila reproductive behaviour". Nature. 451 (7174): 33–37. doi:10.1038/nature06483. ISSN 1476-4687. PMID 18066048.
  9. Yapici, Nilay (2008). Molecular and genetic analysis of Drosophila melanogaster female reproductive behaviours (phd thesis). wien: uniwien.
  10. Kim, Young-Joon; Bartalska, Katarina; Audsley, Neil; Yamanaka, Naoki; Yapici, Nilay; Lee, Ju-Youn; Kim, Yong-Chul; Markovic, Milica; Isaac, Elwyn; Tanaka, Yoshiaki; Dickson, Barry J. (2010-04-06). "MIPs are ancestral ligands for the sex peptide receptor". Proceedings of the National Academy of Sciences. 107 (14): 6520–6525. Bibcode:2010PNAS..107.6520K. doi:10.1073/pnas.0914764107. ISSN 0027-8424. PMC 2851983. PMID 20308537.
  11. , Kim, Young-Joon; Nilay Yapici & Barry Dickson et al., "Method for Controlling Insect Populations", issued 2009-06-11
  12. "YAPICI LAB". YAPICI LAB. Retrieved 2020-04-29.
  13. "NeuroNex—a Radical Collaboration". Cornell Research. 2017-07-17. Retrieved 2020-04-29.
  14. Aragon, Max Jameson; Wang, Mengran; Shea, Jamien; Mok, Aaron T.; Kim, Haein; Lett, Kawasi M.; Barkdull, Nathan; Schaffer, Chris B.; Xu, Chris; Yapici, Nilay (2019-10-09). "Non-invasive multiphoton imaging of neural structure and activity in Drosophila". bioRxiv: 798686. doi:10.1101/798686.
  15. Yapici, Nilay; Cohn, Raphael; Schusterreiter, Christian; Ruta, Vanessa; Vosshall, Leslie B. (2016-04-21). "A Taste Circuit that Regulates Ingestion by Integrating Food and Hunger Signals". Cell. 165 (3): 715–729. doi:10.1016/j.cell.2016.02.061. ISSN 1097-4172. PMC 5544016. PMID 27040496.
  16. Sánchez-Alcañiz, Juan Antonio; Silbering, Ana Florencia; Croset, Vincent; Zappia, Giovanna; Sivasubramaniam, Anantha Krishna; Abuin, Liliane; Sahai, Saumya Yashmohini; Münch, Daniel; Steck, Kathrin; Auer, Thomas O.; Cruchet, Steeve (2018-10-12). "An expression atlas of variant ionotropic glutamate receptors identifies a molecular basis of carbonation sensing". Nature Communications. 9 (1): 4252. Bibcode:2018NatCo...9.4252S. doi:10.1038/s41467-018-06453-1. ISSN 2041-1723. PMC 6185939. PMID 30315166.
  17. Sánchez-Alcañiz, Juan Antonio; Silbering, Ana Florencia; Croset, Vincent; Zappia, Giovanna; Sivasubramaniam, Anantha Krishna; Abuin, Liliane; Sahai, Saumya Yashmohini; Auer, Thomas O.; Cruchet, Steeve; Neagu-Maier, G. Larisa; Sprecher, Simon G. (2018-03-08). "An expression atlas of chemosensory ionotropic glutamate receptors identifies a molecular basis of carbonation detection". bioRxiv: 278804. doi:10.1101/278804.
  18. "Neurobiology professor receives grant for research on hunger | Department of Neurobiology and Behavior Cornell Arts & Sciences". nbb.cornell.edu. Retrieved 2020-04-29.
  19. "American Federation for Aging Research : Nilay Yapici". www.afar.org. Retrieved 2020-04-29.
  20. "NSF awards Cornell $9M grant for neurotech research hub". www.cnybj.com. Retrieved 2020-04-29.
  21. "Nilay Yapici, Ph.D." pew.org. Retrieved 2020-04-29.
  22. "Cornell University". sloan.org. Retrieved 2020-04-29.
  23. Yapici, Nilay; Zimmer, Manuel; Domingos, Ana I. (October 2014). "Cellular and molecular basis of decision-making". EMBO Reports. 15 (10): 1023–1035. doi:10.15252/embr.201438993. ISSN 1469-3178. PMC 4253843. PMID 25239948.
  24. Bussell, Jennifer J.; Yapici, Nilay; Zhang, Stephen X.; Dickson, Barry J.; Vosshall, Leslie B. (2014-07-21). "Abdominal-B neurons control Drosophila virgin female receptivity". Current Biology: CB. 24 (14): 1584–1595. doi:10.1016/j.cub.2014.06.011. ISSN 1879-0445. PMC 4476023. PMID 24998527.
  25. Kim, Young-Joon; Bartalska, Katarina; Audsley, Neil; Yamanaka, Naoki; Yapici, Nilay; Lee, Ju-Youn; Kim, Yong-Chul; Markovic, Milica; Isaac, Elwyn; Tanaka, Yoshiaki; Dickson, Barry J. (2010-04-06). "MIPs are ancestral ligands for the sex peptide receptor". Proceedings of the National Academy of Sciences of the United States of America. 107 (14): 6520–6525. Bibcode:2010PNAS..107.6520K. doi:10.1073/pnas.0914764107. ISSN 1091-6490. PMC 2851983. PMID 20308537.
  26. Häsemeyer, Martin; Yapici, Nilay; Heberlein, Ulrike; Dickson, Barry J. (2009-02-26). "Sensory neurons in the Drosophila genital tract regulate female reproductive behavior". Neuron. 61 (4): 511–518. doi:10.1016/j.neuron.2009.01.009. ISSN 1097-4199. PMID 19249272.


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