Wednesday, April 2, 2025
4/2/2025
Neural Substrates Controlling Metabolic and Reproductive State - Project Summary: The energetics of an organism’s internal biochemical state, or metabolism, are derivative of many factors, but its relationship with the brain remains poorly understood. The goal of this supplement’s parent project is to find new neural substrates that control metabolism using a fly model. To accomplish this, we are in the process of finding neural targets of DN3 neurons that underly metabolic arrest observed during dormancy (Aim 1), identifying heart innervating neurons that appear to be linked to reproductive output (Aim 2), and finding neuropeptides that underly states associated with suppressed anabolism (Aim 3). Dormancy, the focus of Aim 1, is a state of metabolic, reproductive, and developmental arrest. In the fly, dormancy is typically measured by circulating insulin levels, for which we use egg production as a proxy. This state also includes several associated behavioral changes, including a dramatic increase in sleep. Jilian Morejon, a Hispanic-American predoctoral student in the Meiselman lab, has collected preliminary suggesting dormancy-associated sleep has distinct properties and neurochemical underpinnings from diurnal sleep. In this proposal we will assess sleep modulating neurotransmitters and neurons for a secondary role in regulating metabolism and/or controlling state transmission into dormancy. First, we will assess known sleep-inducing agents for their effect on egg production. Next, we will assess glutamate signaling for a role in dormancy. Finally, we will activate and inhibit sleep-modulating neurons in the mushroom body and determine whether reproductive output is affected. Additionally, this supplement will aid in Jilian’s training, helping her reach her ultimate goal of becoming a Principle Investigator conducting biomedical research at a primarily undergraduate institution. Jilian has many strengths, including ability to learn quickly, adaptability, research comprehension, and oratory skills, but also weaknesses which will be addressed in this proposal. Here, we present a plan to develop Jilian as a scientist, thereby diversifying the biomedical workforce. Over this funding period Dr. Matthew Meiselman and Co-Mentor Dr. Eduardo Robledo will improve her proficiency with biological statistics, her niche- specific knowledge base, her engagement with her scientific community, her leadership and professional skills, and guide Jilian to publish her results in a peer-reviewed journal as first-author. Overall, this work will address a major outstanding question of whether sleep and dormancy employ distinct or common neural substrates while permitting the training of an extremely promising predoctoral student.
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