Research Overview
Host:parasite interactions of the malaria parasite, Plasmodium.
Our research interests center on cell surface proteins and adhesive events of the malaria parasite, Plasmodium, as a means toward understanding host:parasite recognition, pathogenesis and virulence. Any parasite protein expressed externally is exposed to host immune surveillance and is therefore, by definition, a vaccine candidate. In this light, functional studies of parasite-derived surface and secreted proteins will additionally aid characterization of candidate molecules of malaria subunit vaccines. Study of the parasite causing malaria is attractive for two principle reasons: the disease is largely neglected, at multiple levels, and is in sore need of a research workforce; and because the great breadth of "malariology", from molecular to human, makes it a fascinating intellectual pursuit. Plasmodium is capable, at various stages in its life cycle, of flagellar motility, slug-like motility and cell-invasive motility. It has a myriad of protein trafficking pathways that dismantle and reform depending on life cycle stage and intra- or extra-cellular stages. Although a single cell, it undergoes numerous transformations between life cycle stages and behaves essentially as a multi-cellular organism via adhesive interactions with host tissues. Plasmodium has male and female gamete stages and fertilizes, the male microgametocyte replicates its genome three times, going from haploid to octaploid, and forms eight flagellar motile microgametes all within a space of 12 minutes - in response to environmental cues after a mosquito takes an infective bloodmeal. The complete Plasmodium genome sequence is now available for annotation; proteomic development; micro-array and gene chip screens and the design of high-throughput functional assays to identify genes encoding extracellular adhesive proteins. We are pursuing the development of post-genomic techniques and taking advantage of gene disruption methodologies to facilitate our understanding of proteins involved in the interface of the malaria parasite Plasmodium and its human and mosquito hosts.
