Identifying Novel Photic Inputs to the Drosophila Circadian/Arousal Neural Network for Behavioral Manipulation

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PROJECT SUMMARY/ABSTRACT Mosquito disease vector control relies mostly on toxic insecticides. A more environmentally friendly alternative is to make use of light-based behavioral manipulation to attract pests to traps and repel pests away from human habitation. The present technology is based on the assumption that mosquito UV light detection occurs solely through opsin-based photoreception in the eyes. The Holmes Lab has recently found additional UV and short wavelength photoreceptive elements expressed in central brain neurons that strongly modulate complex insect behavioral responses to light. Therefore, there is a need to incorporate these additional elements in disease vector control designs for improved efficiency. Namely, CRYPTOCHROME (CRY), which is classically associated with its role in circadian clock resetting, activates with blue- and UV- light and increases the electrical excitability of circadian/arousal neurons. Based on my preliminary data, I hypothesize that CRY coordinates with other photoreceptors to mediate light-induced electrical excitability of neurons, which underlie complex sleep/wake and circadian modulated avoidance/attraction behaviors. My objectives are to determine the mechanism of CRY phototransduction, how we can manipulate that mechanism along with other light inputs to modulate complex behavioral responses to light, and if we can translate that knowledge to a mosquito system for light-based control. I will begin by examining the molecular phototransduction mechanism that underlie CRY-mediated electrical excitability of circadian/arousal neurons in Aim 1. Next, I will measure the relative contribution of different photoreceptor inputs that mediate the electrophysiological photoresponse in circadian/arousal neurons in Aim 2. Last, I will examine the molecular phototransduction mechanism and photic response of transgenic Drosophila expressing day-versus night-biting mosquito CRYs in Aim 3. My research will be useful for developing innovative LED devices for species-specific harmful insect control in the ongoing fight against vector-borne diseases. My Sponsor, Dr. Todd Holmes, and I have developed a training plan to focus on the development of my technical, writing and communication, and mentorship skills. Development of my technical skills will focus heavily on electrophysiology, behavioral assays, and microscopy. I plan to register for relevant courses, attend workshops and training events, and network with experts in the field. Development of my writing and communication skills will be accomplished by applying for grants/fellowship, manuscript development, and presenting at conferences and symposiums. Additionally, I will develop my mentorship skills by training undergraduate students to help run experiments and analyze data. I am a part of a highly collaborative research environment, with many experts in electrophysiology, neurobiology and behavior, microscopy, genetics, and bioinformatics within my department. I plan to fully utilize the resources and facilities available to me in order to accomplish the goals of this proposal, as well as achieve my goal of becoming an independent research scientist.