The protozoan parasites Plasmodium falciparum and Blastocystis: host-pathogen interactionsPlasmodium falciparum is the most virulent of the human malaria parasites and causes the most devastating parasitic disease resulting in about 1-3 million deaths annually. Factors that contribute to its pathogenicity include the radical transformation of the host red blood cells (RBCs) into rigid and adherent structures. Our laboratory is a member of the Global Enterprise for Micro Mechanics and Molecular Medicine (GEM4), and is involved in the use of bioengineering approaches (optical tweezers, atomic force microscopy, microfluidics) to characterize the biomechanical properties of infected cells as a step towards drug discovery and understanding malaria pathogenesis. Our laboratory, together with collaborators at the Division of Bioengineering, is focused on the development of image recognition systems that will facilitate the characterization of malaria-infected blood cells.

Our laboratory has contributed extensively to the current understanding of Blastocystis biology. Our research on this protozoan focuses on host-pathogen interactions, which aims to clarify its controversial role in intestinal disease. We have shown that the parasite exhibits IgA protease activity, induces apoptosis in host cells, and compromises barrier function in intestinal epithelial cells. Current work involves molecular characterization of Blastocystis virulence factors by proteomic and genomic approaches.

Protozoan programmed cell death
We are also studying the phenomenon of programmed cell death (PCD) in protozoan parasites using Blastocystis and P. falciparum as model organisms. Our work on both parasites has shown that a variety of external stimuli can trigger PCD with features similar to those reported for mammalian cells, including links between caspase activation/ mitochondrial factors and DNA fragmentation. We are currently studying the molecules that are involved in the induction and regulation of PCD in B. hominis, with particular focus on caspase-dependent and –independent pathways. A metacaspase homologue has been identified in the P. falciparum genome database and we are investigating its role in malaria PCD. The identification of novel activators of protozoan PCD provide exciting possibilities for anti-parasite strategies.

Tan KSW (2008) New insights on classification, identification, and clinical relevance of Blastocystis spp. Clin. Microbiol. Rev. In Press.

Wawrzyniak I, Roussel M, Diogon M, Couloux A, Texier C, Tan KSW, Vivarès CP, Delbac F, Wincker P and Alaoui HE (2008) Complete circular DNA in the mitochondria-like organelles of Blastocystis hominis. Int. J. Parasitol. In Press.

Lantsman Y, Tan KSW, Morada M and Yarlett N (2008) Biochemical Characterization of a mitochondrial-like organelle from Blastocystis sp. subtype 7. Microbiology. In Press.

Puthia MK, Jia L and Tan KSW (2008) Blastocystis contains cysteine proteases that mediate interleukin-8 response from human intestinal epithelial cells in a NFkB-dependent manner. Eukaryot. Cell. 7:435-43

Wong KH, Ng GC, Lin RT, Yoshikawa H, Taylor MB and Tan KSW (2008) Predominance of subtype 3 among Blastocystis isolates from a major hospital in Singapore.  Parasitol. Res. 102:663-670 

Stensvold CR, Suresh GK, Tan KSW, Thompson RC, Traub RJ, Viscogliosi E, Yoshikawa H and Clark CG (2007) Terminology for Blastocystis subtypes - a consensus. Trends in Parasitol. 23:93-96 

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