OCT-OVA: Finding the mechanism of Octbeta2-dependent mosquito infertility
Lead Research Organisation:
University College London
Department Name: Ear Institute
Abstract
OCT-OVA is an innovative, multi-lab, multi-disciplinary project that straddles both basic and translational science. It aims to investigate how a single neurotransmitter receptor, and highly promising target for vector control, is necessary for viable egg production in female mosquitoes. In the process, OCT-OVA will provide both big data and transgenic resources for the community and give evolutionary insight into what might be a distinct system for the neuromodulation of fertility in a facultative blood-feeder.
Mosquitoes require protein-rich blood in order to lay eggs, and it is this blood-feeding behaviour which leads to the spread of debilitating diseases such as malaria. Once they have acquired a bloodmeal, the process of ovulation begins, followed by fertilisation. We have found that mutation of the gene encoding Octbeta2R leads to a complete disruption of fertilisation. Octbeta2R is a G Protein- Coupled Receptor (GPCR) that is bound by octopamine - a neuroactive molecule that in invertebrates, acts as the functional homologue of adrenergic transmitters. GPCRs are highly "druggable". Molecules that block Octbeta2R could thus act as mosquito contraceptives, preventing them from laying fertile eggs and controlling populations.
However, the cause of this phenotype is unclear. Which cells are responsible for the defect and what do they do? I would like to use state-of-the-art methods to molecularly profile the female mosquito reproductive system. I will then identify clusters of cells that express Octbeta2R, and using transgenic drivers and responders, explore which cell types are responsible for the fertility defect. This project will bridge the gap between genes, circuits and fertility, and reveal how molecular cell state influences organismal reproductive state. Understanding Octbeta2R-dependent mosquito sterility will galvanise the development of much needed mosquito control tools, in line with EU strategies for epidemic management and preparedness.
Mosquitoes require protein-rich blood in order to lay eggs, and it is this blood-feeding behaviour which leads to the spread of debilitating diseases such as malaria. Once they have acquired a bloodmeal, the process of ovulation begins, followed by fertilisation. We have found that mutation of the gene encoding Octbeta2R leads to a complete disruption of fertilisation. Octbeta2R is a G Protein- Coupled Receptor (GPCR) that is bound by octopamine - a neuroactive molecule that in invertebrates, acts as the functional homologue of adrenergic transmitters. GPCRs are highly "druggable". Molecules that block Octbeta2R could thus act as mosquito contraceptives, preventing them from laying fertile eggs and controlling populations.
However, the cause of this phenotype is unclear. Which cells are responsible for the defect and what do they do? I would like to use state-of-the-art methods to molecularly profile the female mosquito reproductive system. I will then identify clusters of cells that express Octbeta2R, and using transgenic drivers and responders, explore which cell types are responsible for the fertility defect. This project will bridge the gap between genes, circuits and fertility, and reveal how molecular cell state influences organismal reproductive state. Understanding Octbeta2R-dependent mosquito sterility will galvanise the development of much needed mosquito control tools, in line with EU strategies for epidemic management and preparedness.
