Neural Substrates Controlling Metabolic and Reproductive State

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PROJECT SUMMARY The goal of this project is to find new neural substrates governing metabolic state in Drosophila melanogaster. Success of organisms through evolutionary time depends upon their ability to optimize utilization of resources. When environments become unfavorable, animals will preserve energy and attenuate reproduction. This strategy requires perception and assessment of a complex environment, which is an ancient role of the nervous system. Many metabolic disorders in humans, such as polycystic ovarian syndrome, remain incompletely understood, but probing an underlying role for the nervous system remains a monumental challenge. Here, we propose to exploit the genetic accessibility and cellular resolution experiments possible in the fly, Drosophila melanogaster, to explore how the brain sets metabolic and reproductive state. Given the importance of environmental adaptation, we expect the biological principles underlying these strategies to be highly conserved among motile animals with nervous systems, including flies and humans. The Meiselman lab seeks to establish a network map for the nervous system components that permit the fly brain to change metabolic state, thereby laying groundwork for investigations in organisms with brains of higher complexity. During my postdoc I showed that DN3 circadian neurons and expression of their operant neuropeptide, Allatostatin-C (AstC), are temperature-sensitive and terminate cold-induced reproductive arrest when warm temperatures return. In this proposal, we will find the minimal neural subset that depends on temperature information from DN3s and adjusts reproductive output, then examine how their innate activity responds to temperature change with calcium imaging (Aim 1.1). Next, we will determine if the minimal subset controlling reproduction causes changes to rhythmicity, feeding, and metabolic rate (Aim 1.2). We will then investigate a second subset of neurons that depress reproduction when activated, heart-innervating LkAC neurons. We will assess their role in modulation of metabolism (Aim 2.1) and examine if their activity affects heartbeat (Aim 2.2). Finally, we will find the molecular (Aim 3.1) and neural (Aim 3.2) substrates that attenuate reproduction in response to noxious percepts (hunger, thirst, and high heat). In sum, this work will offer comprehensive insight into how the nervous system integrates sensory information to control metabolic state and reproduction. This project will present opportunities for diverse students at a minority-serving institution (UNLV) to engage in research which utilizes cutting-edge techniques. My co-mentors Dr. Mariana Wolfner and Dr. Frank van Breukelen, and collaborators Drs. Allen Gibbs and Nilay Yapici collectively have world-leading expertise in fly genetics, metabolism, and neurobiology. Their support will allow me to foster a successful laboratory environment wherein I can offer top notch mentorship to my students and reach my career goals. In addition to critical technical skills, my mentors will offer me guidance that will allow me to establish a successful extramurally funded research program, and to unveil new insights into the interface between brain and metabolic state.