Current Research Interests
I am a postdoctoral fellow in the Kafatos/Christophides lab at Imperial College London. My research focuses on how the innate immune system of the mosquito recognizes and eliminates malaria parasites. Though it is not widely known, mosquitoes are amazing parasite killers. In fact, the vast majority of the parasites ingested when a mosquito bites a malarious person are attacked and eliminated before they can mount an infection. It is the few parasites that survive (one is enough), that are ultimately responsible for disease transmission.
The mosquito has multiple lines of defense, but the most potent is found in its blood (hemolymph). Parasites contact the mosquito blood when they cross the gut cells as they try to escape the harsh digestive conditions of the gut lumen. Two Leucine-rich repeat (LRR) containing proteins, LRIM1 and APL1C, orchestrate the mosquito immune defense. We recently found that these proteins circulate in the mosquito hemolymph in a disulfide-bonded multimeric complex . If either LRIM1 or APL1C is knocked-down by RNAi the complex is lost from the hemolymph. Before parasites are killed, the complement-like protein TEP1 is localized on their surface, marking them for destruction. The LRIM1/APL1C complex interacts with the complement-like protein TEP1 and is required for TEP1 localization to parasites during midgut invasion. When the LRIM1/APL1C complex is knocked-down by RNAi, TEP1 fails to localize and the invading parasites are not killed. This immune pathway leading to parasite killing can be an important cause of natural refractoriness in non-vector mosquitoes . Fully understanding the mechanism of parasite killing and why some parasites manage to escape may open the door to novel control strategies.
We found that LRIM1 and APL1C are defining members of a protein family, named LRIMs (pronounced L-rims) . Bioinformatic searches using specific features shared between LRIM1 and APL1C has uncovered approximately 20 family members falling into four distinct sub-families in Anopheles gamibae, Aedes aegypti and Culex quinquefasciatus but none in any other organisms. Given the central role of LRR proteins in host defense in plants and animals, we are currently investigating the hypothesis that the repertoire of LRIMs may help the mosquito neutralize diverse pathogens, including the agents of human and animal diseases that they transmit.
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