Characterization of the mosquito midgut immunity landscape and identification of novel antimicrobial peptides
File(s)
Author(s)
Cai, Julia
Type
Thesis
Abstract
Malaria is a preventable disease which continues to impact a quarter of a billion people annually. It is caused by Plasmodium parasites, which can be transmitted to humans through the bites of female Anopheles mosquitoes. Numerous intervention strategies have been deployed to curb the spread of malaria, including the use of insecticides, drugs, and a vaccine. While these strategies have successfully reduced incidences of malaria, progress has stalled due to a variety of limitations, particularly the spread of insecticide resistance within mosquito populations. Therefore, novel intervention strategies must be explored and implemented. One promising area of research is the generation of malaria-refractory transgenic mosquitoes. Host-parasite interactions taking place in the mosquito midgut could be a critical component of developing such interventions, as the parasite undergoes a major bottleneck in this tissue during their development. In the midgut, a battery of immune responses contribute to this natural bottleneck, including the production of antimicrobial peptides (AMPs). Thus, better characterization of these midgut immune responses could enable the usage of these effectors and/or their loci in the blockade of malaria transmission. Transcriptome analyses were performed on mosquito tissues which enabled the characterization of spatiotemporal expression profiles for all genes in response to blood feeding and malaria infection, in addition to the identification of novel, putative AMPs. A clear dichotomy was detected in the midgut, where more anterior regions invest significant amounts of resources into immunity compared with digestion in the more posterior regions. These functions persist even in the absence of an immune stimulus. It is proposed that the functional polarity of the midgut is underpinned by concentration gradients of different transcription factors in a manner similar to development patterning along a tissue axis. These data can inform the generation of future transgenic mosquitoes for use in a novel malaria intervention strategy.
Version
Open Access
Date Issued
2023-12
Date Awarded
2024-03
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
Christophides, Prof. George
Vlachou, Dr. Dina
Publisher Department
Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)