Contact Information

Address: 51 Newton Road, 4-403 BSB
Iowa City, IA 52242 Email: john-donelson@uiowa.edu

Research

Our laboratory seeks to understand how gene expression is regulated in pathogens that cause the major tropical diseases of the world, such as trypanosomiasis, leishmaniasis and malaria. These parasitic organisms evade the human immune system using sophisticated molecular mechanisms that are based on the appearance of unique surface proteins at the proper times during infection.  Our goal is to determine at the DNA and RNA levels how these parasites developmentally regulate the production of these surface proteins in anticipation that this information will help to eliminate or better control these diseases.

One project involves a characterization of gene rearrangements that occur in African trypanosomes. These protozoan parasites are transmitted by tsetse flies to the bloodstream of humans and animals where they cause a fatal disease called trypanosomiasis or sleeping sickness. They avoid their host’s immune system by periodically switching their major surface protein, a process called antigenic variation. A given trypanosome population can sequentially expression hundred of these different variant surface glycoproteins (VSGs) as it continually escapes the antibodies directed against it. We have isolated the genes for many of these VSGs and demonstrated that gene duplications often govern the selection of a specific VSG gene to be transcribed while excluding all of the other VSG genes from expression. The expressed, duplicated gene is always located near a chromosomal telomere. We are studying the promoters that are located within these telomere-linked VSG gene expression sites, and examining possible mechanisms responsible for the VSG duplications. We are also investigating the chromatin organization and nuclear localizations of these expression sites.

Another project focuses on the genes for the Major Surface Protease (MSP; also called glycoprotein 63 or GP63) located on the surface of Leishmania chagasi, a protozoan parasite that causes visceral leishmaniasis in many tropical regions of South America. This organism avoids the human immune system by invading macrophages – the very cells of the immune system designed to recognize and destroy foreign pathogens. MSP participates in the parasite’s invasion of macrophages and contributes to its survival within the macrophage. We have found that Leishmania actually has multiple forms of MSP that are expressed at different stages of its life cycle and probably serve different functions. The different MSP forms are encoded by related genes that are regulated post-transcriptionally, i.e., after the initial precursor RNA is synthesized. We are using a variety of biochemistry and cell biology techniques to examine the molecular mechanisms of this post-transcriptional and translational control of the different MSP genes.

Selected Publications

  Yao C, Gaur Dixit U, Barker JH, Teesch LM, Love-Homan L, Donelson JE, Wilson ME. (2013) Attenuation of Leishmania infantum chagasi metacyclic promastigotes by sterol depletion. Infect Immun. 81(7):2507-17. DOI: 10.1128/IAI.00214-13. PMID: 23630964 

Weirather JL, Wilson ME, Donelson JE. (2012) Mapping of VSG similarities in Trypanosoma brucei. Mol Biochem Parasitol. 181(2):141-52. PMID: 22079099

Reiling L, Richards JS, Fowkes FJ, Wilson DW, Chokejindachai W, Barry AE, Tham WH, Stubbs J, Langer C, Donelson J, Michon P, Tavul L, Crabb BS, Siba PM, Cowman AF, Mueller I, Beeson JG. (2012) The Plasmodium falciparum erythrocyte invasion ligand Pfrh4 as a target of functional and protective human antibodies against malaria. PLoS One. 7(9):e45253. DOI: 10.1371/journal.pone.0045253. PMID: 23028883

Eyford, B.A., Sakurai, T., Loveless, B., Hertz-Fowler, C., Donelson, J.E., Inoue, N., Pearson, T.W. (2011). Differential protein expression throughout the life cycle of Trypanosoma congolense, a major parasite of cattle in Africa. Mol. Biochem. Parasit. 117:116-125.

Debroy, S., Keenan, A.B., Ueno, N., Jeronimo, S.M., Donelson, J.E., Wilson, M.E. (2010). Leishmania infantum chagasi: A genome-based approach to identification of excreted/secreted proteins. Exptl. Parasitol. 126:582-91.

Yao, C., Li, Y., Donelson, J.E., Wilson, M.E. (2010). Proteomic examination of Leishmania chagasi plasma membrane proteins: contrast between avirulent and virulent (metacyclic) parasite forms. Proteomics Clin Appl. 4:4-16.

Helm, J., Hertz-Fowler, C., Aslett, M., Sanders, M., Quail, M.A., Soares, M.B., Bonaldo, M.F., Sakurai, T., Inoue, N., Donelson, J.E. (2009). Analysis of expressed sequence tags from the four main developmental stages of Trypanosoma congolense. Mol. Biochem. Parasitol. 168:34-42.

Helm, J., Wilson, M.E., Donelson, J.E. (2009). Differential expression of a protease gene family in African trypanosomes. Mol. Biochem. Parasitol. 163:8-18.

Helm, J., Wilson, M.E., Donelson, J.E. (2008) Different trans RNA splicing events in bloodstream and procyclic Trypanosoma brucei. Mol. Biochem. Parasitol. 159:134-137.

Yao C., Chen Y., Sudan B., Donelson, J.E., Wilson, M.E. (2008) Leishmania chagasi: Homogenous metacyclic promastigotes isolated by buoyant density are highly virulent in a mouse model. Exptl. Parasitol. 118:129-133.

Donelson, L.G., Donelson, J.E. (2008) Review of "The fatal sleep: Africa's killer disease that went undiscovered for centuries," Luath press LTD, United Kingdon. J. Clin. Invest. 118:393.

Hsiao C.-H.C., Yao, C., Storlie, P., Donelson, J.E., Wilson, M.E. (2008) The major surface protease (MSP or GP63) in the intracellular amastigote stage of Leishmania chagasi. Mol. Biochem. Parasitol. 157:148-159

Grandgenett P.M., Otsu K., Wilson, H.R., Wilson, M.E., Donelson, J.E. (2007) A function for a specific zinc metalloprotease of African trypanosomes. PLoS Pathogens 3:1432-1445.

Yao C., Donelson, J.E., Wilson M.E. (2007) Internal and surface-localized MSP of Leishmania and their differential release from promastigotes. Eukaryot Cell 6:1905-1912.

Yao, C., Luo, J., Hsiao, C-H., Donelson, J.E. and Wilson, M.E. (2007) Leishmania chagasi: A tetracycline-inducible cell line driven by T7 RNA polymerase. Exp Parasitol. 116:205-213.

Martins, D.R., Jeronimo, S.M.B., Donelson, J.E., and Wilson, M.E. (2006) Leishmania chagasi T-cell antigens identified through a double library screen. Infect. Immun. 74:6940-6948.

Montagna, G.N., Donelson, J.E., and Frasch, A.C.C. (2006) Procyclic Trypanosoma brucei expresses separate sialidase and trans-sialidase enzymes on its surface membrane. J. Biol. Chem. 281:33949-33958.

Berriman, M., Ghedin, E., and Donelson, J.E., et al. (2005) The genome of the African Trypanosome Trypanosoma brucei. Science 309:416-422.

Yao, C., Luo, J., Hsiao, C., Donelson, J.E., and Wilson, M.E. (2005) Internal and surface subpopulations of the major surface protease (MSP) of Leishmania chagasi. Mol. Biochem. Parasitol. 139:173-183.

El-Sayed, N.M, Myler, P.J. and Donelson, J.E., et al. (2005) Comparative genomics of trypanosomatid parasitic protozoa. Science 309:404-409.

Purdy, J.E., Donelson, J.E., and Wilson, M.E. (2005) Leishmania chagasi: The α-tubulin intercoding region results in constant levels of mRNA abundance despite protein synthesis inhibition and growth state. Exp. Parasit. 110:102-107.

Purdy, J.E., Doneslon, J.E., and Wilson, M.E. (2005) Regulation of genes encoding the major surface protease of Leishmania chagasi via mRNA stability. Mol. Biochem. Parasitol 142:88-97.

Lincoln, L.M., Ozaki, M., Donelson, J.E., and Beetham, J.K. (2004) Genetic complementation of Leishmania deficient in PSA (GP46) restores their resistance to lysis by complement. Mol. Biochem. Parasitol. 137:185-189.

Yao, C., Luo, J., Storlie, P., Donelson, J.E., and Wilson, M.E. (2004) Multiple products of Leishmania chagasi major surface protease (MSP or GP63) gene family. Mol. Biochem. Parasitol. 135:171-83.

Barrett, B., LaCount, D.J., and Donelson, J.E. (2004) A first-generation CRE-loxP site-specific recombination system in African trypanosomes. Exp. Parasitol. 106:37-44.

DaRocha, W.D., Otsu, K., Teixeira, S.M.R., and Donelson, J.E. (2004) Tests of cytoplasmic RNA interference (RNAi) and construction of a tetracycline-inducible T7 promoter system in Trypanosoma cruzi. Mol. Biochem. Parasitol. 133:175-186.