Abstract

: Plasmodium sporozoites migrate through and invade different cell types in the mosquito vector and vertebrate host. At the end of their journey they transform into exo-erythrocytic forms within a hepatocyte. Irradiated sporozoites induce protective immunity against malaria and therefore it is of great importance to identify sporozoite and EEF proteins entering the host hepatocyte. However, little is known about secreted and surface proteins of Plasmodium sporozoites and their involvement in sporozoite-host cell interactions. No information is available about proteins involved in the cross talk of the intracellular EEF with the host hepatocyte. The overall objective of this proposal is the characterization of newly identified sporozoite-expressed and EEF-expressed proteins and their role in host-parasite interactions and the identification of additional molecules that could be important for these interactions. This will lead to a more complete understanding of the parasites complex biology but might also identify new potential candidates for inclusion into a pre-erythrocytic subunit vaccine and targets for transmission blocking strategies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI053709-05
Application #
6986767
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Rogers, Martin J
Project Start
2002-12-15
Project End
2007-11-30
Budget Start
2005-12-01
Budget End
2006-11-30
Support Year
5
Fiscal Year
2006
Total Cost
$326,396
Indirect Cost

  Institution

Name
Seattle Biomedical Research Institute
Department
Type
DUNS #
070967955
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Arredondo, Silvia A; Kappe, Stefan H I (2017) The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle. Int J Parasitol 47:409-423
Groat-Carmona, Anna M; Kain, Heather; Brownell, Jessica et al. (2015) A Plasmodium ?/?-hydrolase modulates the development of invasive stages. Cell Microbiol 17:1848-67
Lindner, Scott E; Swearingen, Kristian E; Harupa, Anke et al. (2013) Total and putative surface proteomics of malaria parasite salivary gland sporozoites. Mol Cell Proteomics 12:1127-43
Pei, Ying; Miller, Jessica L; Lindner, Scott E et al. (2013) Plasmodium yoelii inhibitor of cysteine proteases is exported to exomembrane structures and interacts with yoelipain-2 during asexual blood-stage development. Cell Microbiol 15:1508-1526
Vaughan, Ashley M; Kappe, Stefan H I; Ploss, Alexander et al. (2012) Development of humanized mouse models to study human malaria parasite infection. Future Microbiol 7:657-65
Lindner, Scott E; Miller, Jessica L; Kappe, Stefan H I (2012) Malaria parasite pre-erythrocytic infection: preparation meets opportunity. Cell Microbiol 14:316-24
MacKellar, Drew C; Vaughan, Ashley M; Aly, Ahmed S I et al. (2011) A systematic analysis of the early transcribed membrane protein family throughout the life cycle of Plasmodium yoelii. Cell Microbiol 13:1755-67
Vaughan, Ashley M; Wang, Ruobing; Kappe, Stefan H I (2010) Genetically engineered, attenuated whole-cell vaccine approaches for malaria. Hum Vaccin 6:107-13
Mackellar, Drew C; O'Neill, Matthew T; Aly, Ahmed S I et al. (2010) Plasmodium falciparum PF10_0164 (ETRAMP10.3) is an essential parasitophorous vacuole and exported protein in blood stages. Eukaryot Cell 9:784-94
Jacobs-Lorena, Vanessa Y; Mikolajczak, Sebastian A; Labaied, Mehdi et al. (2010) A dispensable Plasmodium locus for stable transgene expression. Mol Biochem Parasitol 171:40-4

Showing the most recent 10 out of 15 publications