Genetic methods to control protein levels are extremely valuable tools for probing the basic biology of any organism. Two commonly employed tools are RNA interference and conditional expression, neither of which has been successfully implemented in malaria research. We are developing a new method to control proteins in the secretory pathway of malaria parasites. Over 20% of the proteins encoded by the Plasmodium falciparum genome are thought to pass through the secretory system on their way to organellar or extracellular destinations. These proteins have key roles in parasite metabolism, nutrient acquisition, invasion, host cell remodeling, and other critical aspects of parasite biolog. The goal of this project is to design and optimize a conditional probe to control the localization f soluble secretory proteins in P. falciparum. This method will then be validated by applying it to two biological targets: one in the apicoplast organelle and one which resides in the parasitophorous vacuole. Successful development of a conditional localization tool will enhance our ability to probe the basic biology of malaria parasites and will allow us to validate potential targets for therapeutic intervention.

Public Health Relevance

The inevitable rise of drug-resistant malaria parasites creates a continuing need to develop new control strategies. We are developing a genetic tool that will help to probe basic parasite biology and validate new drug targets.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI101589-01
Application #
8360966
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Mcgugan, Glen C
Project Start
2012-06-20
Project End
2014-05-31
Budget Start
2012-06-20
Budget End
2013-05-31
Support Year
1
Fiscal Year
2012
Total Cost
$237,730
Indirect Cost
$87,730
Name
Johns Hopkins University
Department
Microbiology/Immun/Virology
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Dellibovi-Ragheb, Teegan A; Gisselberg, Jolyn E; Prigge, Sean T (2013) Parasites FeS up: iron-sulfur cluster biogenesis in eukaryotic pathogens. PLoS Pathog 9:e1003227