Mosquitoes transmit multiple diseases of enormous health importance worldwide, and research to fundamentally understand the reproductive biology of mosquitoes is critical to population control efforts for these deadly disease vectors. While RNA-binding proteins (RBPs) play central roles in early development in model insect systems, very little is known about the function of RBPs in mosquito reproduction, and significant differences with the insect models are expected. In this study, we will address this knowledge gap using a combination of bioinformatic, genetic and molecular biology approaches. In preliminary data, integrative bioinformatic analysis has identified a focused set of RBPs with candidate roles in mosquito oocyte and embryo development. We will investigate their function in Aedes aegypti through the use of RNA interference and CRISPR/Cas9 tag knock-in lines, and will employ cutting-edge molecular profiling methods and integrative analysis to assess the impact of relevant RBPs on the mRNA lifecycles. Investigating RBP function in mosquito reproduction is highly significant because it would identify novel attractive targets for gene drive efforts. Additionally, since our understanding of post-transcriptional gene regulation lags behind that of transcriptional control in most systems, this novel and largely unstudied aspect of mosquito biology will advance our general knowledge of the roles and mechanisms of RBPs in development.
Mosquitoes transmit a number of deadly human diseases, and targeting the mosquito reproductive cycle is an attractive strategy to control their population. In other insects, a class of proteins that are involved in binding and controlling messenger RNA lifecycles (RNA-binding proteins) plays a critical role in reproduction, specifically oocyte and embryo development. However, the roles of RNA-binding proteins in mosquito development are largely unknown, and we propose to investigate the roles of this class of proteins in mosquitoes to better understand their developmental biology and to derive novel targets for population control efforts.
