Peptide regulation of mosquito blood feeding and mating

Project Summary Mosquitoes are obligate blood-feeders that pose increasing threats to global public health by spreading the pathogens that cause diseases, including Zika and malaria, among humans. Blood-feeding and mating behaviors play key roles in vector biology and undergo dramatic changes influenced by environmental cues and internal state but we know little about the physiological changes underlying the behavioral readout. Neuropeptide signaling pathways are ancient and conserved regulators of feeding and reproduction in many animals, including mosquitoes. The long-term objectives of this research are to define the mechanisms by which neuropeptide signaling coordinates organismal physiology in mosquitoes to regulate blood- feeding and reproduction. Building on recent breakthroughs that have allowed us to genetically disrupt critical neuropeptide pathways and manipulate the cells that express these genes, we will use an innovative combination of pharmacological and genetic techniques to ask how specific neuropeptides coordinate organismal physiology to coordinate these innate behaviors. The drive to blood feed is not constitutive; female mosquitoes suppress their drive to bite humans at specific times of day, during blood digestion, and egg development. Although it is clear that nutrient sensing, oocyte development, and circadian signals influence each other, exactly how these individual components combine to temporally regulate mosquito attraction to humans remains unknown. We will determine how cellular responses and behavioral features of host-seeking are regulated by circadian and satiety-related neuropeptide pathways. Mating and reproductive behaviors also show variation by time of day and female physiological state. Female mating receptivity is regulated by signals, including neuropeptides, that are transferred from males to females during mating. These signals suppress female receptivity for the rest of her lifetime and allow her to allocate nutritional resources for reproduction. We will ask how neuronal, physiological, and behavioral responses to mating signals change by time of day and female mating status and determine how neuropeptides control these responses by evaluating females with disrupted circadian and mating-related neuropeptide signaling pathways. These results will provide the basis for novel approaches to mosquito control since targeting the receptors that affect biting and reproduction could be "weaponized" against mosquitoes to disrupt these behaviors.