Our laboratory couples molecular parasitology and structural biology to study the malaria parasite (Plasmodium spp.). Malaria is still one of the great global health challenges today. Conservative estimates from the World Health Organization indicate that, every year, about 500 million people become infected, and of these people nearly 1 million people will die from their infection. Significant efforts have been made to develop new drugs and vaccines, however, the mounting resistance to these drugs and the limited efficacy of the current generation of vaccines have not allowed for the goals of elimination and eradication of the parasite to be met.
In response to this, our laboratory conducts Discovery Phase research using the mouse-infective malaria parasite Plasmodium yoelii in three key areas that focus upon crucial aspects of the parasite’s growth, development, and transmission.
1. Translational Regulation During Parasite Transmission
Our group is building upon our previous work that uncovered the importance of specific protein/RNA complexes for the maintenance of parasite infectivity during transmission from a mosquito to a mammal. This work is supported by a K22 Research Scholar Development Award from the NIAID, and will push the practical and technical boundaries of doing practical biochemistry with the sporozoite stage of the malaria parasite. Through this work, we hope to uncover how the parasite produces and maintains this latent infectious state as it awaits the unpredictable moment of transmission from the mosquito.
2. Transcriptional Regulation by Specific Transcription Factors
In collaboration with Dr. Manuel Llinás, we have produced the first x-ray crystallographic model of an ApiAP2 specific transcription factor bound to its cognate double-stranded DNA binding site. Additional research has demonstrated that this family of proteins is widely important, as they function to regulate the parasite’s gene expression dynamics both generally and during specific developmental stages. Through this work with Dr. Llinás, we hope to further characterize these key regulatory mechanisms by building upon our atomic-level understanding of the ApiAP2 protein family.
3. Comprehensive Proteomics
In collaboration with Drs. Stefan Kappe, Robert Moritz and Photini Sinnis, our Bill and Melinda Gates Foundation supported work has produced the most comprehensive total proteome of a mosquito stage parasite (salivary gland sporozoite) to date. Additionally, we have adapted labeling techniques to identify novel surface proteins of the salivary gland sporozoite, which may prove to be valid candidates for antibody-based vaccines. Through this collaborative work, we hope to identify the dynamics of protein utilization during infection to exploit these events therapeutically.