Bio:
I am a third year JHMI BCMB (Biochemistry, Cellular, and Molecular Biology) graduate student. I did my undergraduate studies at Erskine College in South Carolina, where I received BS degrees in Biology and Chemistry. I joined the Dimopoulos Group in June 2009 and have a very excited project aimed to explore and molecularly characterize the mosquito's innate immune response to Plasmodium falciparum, the causal agent of human malaria. Please see below my PhD thesis proposal and studies I am undertaking.

Current research:

Dissecting the tripartite interactions between the mosquito Anopheles innate immune system, the microbiota, and the malaria parasite Plasmodium falciparum.

Caudal controls vector competence for Plasmodium falciparum as a regulator of the tripartite interactions between the innate immune system, the microbiota and the malaria parasite

Anopheles gambiae is the major African mosquito vector for the human malaria parasite Plasmodium falciparum. The innate immune system of the mosquito is able to defend against Plasmodium infection mainly via the Toll and Imd (Immune Deficiency) signaling pathways, which when elicited can upregulate AMP (antimicrobial peptide) production and other immune-derived effectors that act against Plasmodium. Previous research has shown that the Imd pathway more efficiently defends against the human malaria parasite P. falciparum than the rodent malaria parasite P. berghei (Garver et al., 2009). Interestingly, mosquito immune defenses are also mediated by the microbiota present in the mosquito midgut, which is the primary site for Plasmodium invasion and development (Dong et al., 2006 & 2009). Thus, I am currently investigating the role of Caudal (Cad) in A. gambiae innate immunity to further dissect potential correlations between the mosquito’s antibacterial and anti-Plasmodium responses and the mosquito’s midgut microbiota. In Drosophila, Caudal is a developmental transcription factor as well as an Imd innate immune repressor of AMP gene expression and regulator of midgut homeostasis (Ryu et al., 2008). Since the innate immune signaling pathways are majorly conserved among Drosophila and Anopheles, I hypothesize that Cad in An. gambiae may also similarly modulate the midgut microbiota and thereby influence Plasmodium infection and development in the mosquito midgut. Towards this end, I propose the following research aims and questions:

Specific Aim 1: What is Cad’s role in midgut microbiota homeostasis?
Influence on midgut microbiota proliferation and species composition

Specific Aim 2: What is Cad’s influence on the Anophelise innate immune response to Plasmodium infection?
Plasmodium’s development in mosquito midgut
- P. falciparum (Imd-regulated; human malaria) vs. P. berghei (Toll-regulated; rodent malaria) development.

Specific Aim 3: Is Cad functioning as an immune factor solely in the Imd signaling pathway?Is Cad functioning as an immune factor solely in the Imd signaling pathway?
Analyses of Toll and Imd transcriptomes upon knockdown of Cad
- Transcriptional regulation of key immune factor genes
Gram- (Imd) and Gram+ (Toll) bacterial challenge and survival

Specific Aim 4: Can Cad be used to develop vector resistance to Plasmodium infection?
Use of A. stephensi Rel2 transgenics
- Cad-KD’s influence on Plasmodium development
Development of Cad transgenics
- Heritable and inducible RNAi
- Investigate resistance to Plasmodium infection

Summary
RNAi-based silencing assays that depletion of the A. gambiae Caudal results in a significant reduction of the midgut microbiota as well as a change of its species composition. Interestingly, Caudal is also a highly potent regulator of vector competence for P. falciparum while its implication in the defense against the rodent parasite P. berghei was weak. These findings suggest that the A. gambiae Caudal controls the finely tuned tripartite interactions between the innate immune system, the midgut microbiota, and the Plasmodium parasite as a factor of the Imd pathway. We are currently conducting comprehensive whole-genome microarray studies to better understand Caudal’s relationship to the Imd and Toll pathways and to identify potent anti-Plasmodium effectors that are transcriptionally controlled by this immune regulator. We also are currently analyzing studies on Caudal’s role in regulating the midgut microbial load and composition in field-derived Anopheles arabiensis mosquitoes, a key vector of malaria in southern Zambia.

Further understanding of the interactions among the Anopheline innate immune response and the microbiome in the modulation of Plasmodium development will allow for the innovative development of novel vector control strategies.