Identification of mosquito brain neurons that drive blood-feeding behavior

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PROJECT SUMMARY Mosquitoes transmit numerous pathogens to humans by virtue of their ability to locate and bite vertebrates. Current strategies to prevent these diseases face various limitations and new approaches are needed. One possibility would be to inhibit the neurons in the mosquito brain that direct the behavior of attraction to humans and feeding on blood, but such neurons have not been identified because the tools and knowledge to do so do not exist. This proposal describes my plan to use genetic and sequencing-based approaches to identify the neurons that are required for blood-feeding behavior. I will take advantage of the fact that mosquitoes require multiple human-derived cues, particularly heat and CO2, to engorge on blood. Using gene expression changes in single cells, I will identify neurons that show altered responses specifically in the presence of both stimuli. To enable the genetic targeting of specific cell types of interest, we will create an atlas of enhancer elements that are specific to each cell type in the mosquito brain, using paired single cell RNA and ATAC-seq data. Finally, we will target key neurons for blood feeding using an enhancer driver constructs and combine them with genetic effectors to test whether the neurons are necessary and sufficient for blood feeding behavior. This proposal combines my expertise in computational genomics, transgenic mosquitoes, and behavior to achieve the goal of identifying neurons at a key node in the neural circuits for blood feeding. The identification of these neurons that drive blood feeding would be useful for understanding how they are activated and thus allow the design of more attractive mosquito traps. These neurons, if inactivated, would prevent mosquitoes from biting humans so they also could serve as a potential target to disrupt the spread of mosquito borne illness.