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. Widely considered to be passive carriers of malaria, mosquitoes are actually 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 (even one is sufficient), that are ultimately responsible for disease transmission.
The mosquito has multiple lines of defense against invading pathogens, but the most potent is found in its blood, called hemolymph. Parasites migrate through the gut epithelium in order to escape the harsh digestive conditions of the gut lumen. Here they come into contact with the hemolymph. Two leucine-rich repeat (LRR) containing proteins, LRIM1 and APL1C, are essential for mosquito immune defense in this compartment. We recently found that these proteins circulate in the mosquito hemolymph in a disulfide-bonded multimeric complex (Povelones, 2009). If either LRIM1 or APL1C is knocked-down by RNAi, the entire complex is lost and parasite survival is increased. Before parasites are killed, the complement-like protein TEP1 is localized on their surface, marking them for destruction. The LRIM1/APL1C complex interacts with TEP1 and is required for its localization to parasites during midgut invasion. When the LRIM1/APL1C complex is knocked-down, TEP1 fails to localize and the invading parasites are not killed. This immune pathway leading to parasite killing could be an important cause of natural refractoriness in non-vector mosquitoes (Habtewold, 2008). Understanding the mechanism of parasite killing, and how some parasites manage to escape, may open the door to novel control strategies.
Additionally, we have found that LRIM1 and APL1C are defining members of a protein family, collectively named LRIMs (pronounced L-rims) (Povelones, 2009). Bioinformatic searches using specific features shared between LRIM1 and APL1C has uncovered approximately 20 family members falling into four distinct sub-families in the mosquito species Anopheles gambiae, Aedes aegypti and Culex quinquefasciatus. This family is not found in any other organism. 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.