Our laboratory is investigating the biology of trypanosomes, protozoan parasites responsible for important tropical diseases. We focus on two areas:

Kinetoplast DNA

Trypanosome mitochondrial DNA consists of several thousand DNA rings topologically interlocked in a giant DNA network. We are studying the novel mechanism by which kinetoplast DNA replicates, the structure of isolated kinetoplast DNA, and the complex structural organization of this network in vivo. Much of our current work concerns the identification and study the proteins involved in kDNA replication and maintenance.

Trypanosome fatty acid synthesis

Trypanosomes have an abundant GPI-anchored protein named variant surface glycoprotein. This GPI anchor is unusual in that it contains the fatty acid myristate. In studies on the origin of myristate, we discovered a robust fatty acid synthesis system whose major product is myristate (even though it was thought for 30 years that these parasites cannot make any fatty acid). In an investigation of the machinery for fatty acid synthesis we discovered a novel and unprecedented mechanism. Instead of using a conventional type I or type II synthase, found in all other cells, trypanosomes use microsomal elongases to make fatty acids de novo. They also have a type II fatty acid synthase in the mitochondria.

Publications:

Zhao, Z., Lindsay, M.E., Robinson, D.R., Englund, P.T. (2008) p166, a link between the trypanosome mitochondrial DNA and flagellum, mediates genome segregation. EMBO J. 27, 143-154.
PubMed Reference

Guler, JL, Kriegova, E., Smith, TK, Lukes, J, Englund, P.T. (2008) Mitocondrial fatty acid synthesis is required for normal mitochondrial morphology and function in Trypanosoma brucei. Mol. Microbiol 67, 1125-42.
PubMed Reference

Liu, Y. and Englund, P.T. (2007) The rotational dynamics of kinetoplast DNA replication. Molecular Microbiology 64.676-690.
PubMed Reference

Stephens, J.S., Lee, S-H, Paul, K.S., and Englund, P.T. (2007) Mitochondrial fatty acid synthesis in Trypanosoma brucei. J. Biol. Chem. 282, 4427-36.
PubMed Reference

Lee, S-H, Stephens, J.L., Paul, K.S., Englund, P.T. (2006) Fatty acid synthesis by elongases in trypanosomes. Cell 126, 691-99.
PubMed Reference

Liu, B., Molina, H., Kalume, D., Pandey, A., Griffith, J.D., and Englund, P.T. (2006) The role of p38 in replication of Trypanosoma brucei kinetoplast DNA Mol. Cell. Biol. 26, 5382-93.
PubMed Reference

Liu, B., Liu, Y., Motyka, S.A., Agbo, E.E.C., and Englund, P.T. (2005) Fellowship of the rings: the replication of kinetoplast DNA. Trends Parasitol. 21, 363-9.
PubMed Reference