Malaria is a leading cause of human death and illness, causing over 300 million cases of clinical malaria and 1+ million deaths each year. Traditional measures to control and cure malaria are becoming increasingly less effective and there is an urgent need for the development of new drugs and vaccines. A strategic hurdle for development of new anti-malarial therapeutics remains the lack of experimentally validated functional information about most P. falciparum genes. Critical for identification of new drug targets is a better understanding of essential metabolic pathways and weaknesses in the parasite's physiology. Our approach will create a large library of P. falciparum parasite mutant clones with single piggyBac insertions that will be used for phenotypic analysis. Preliminary studies have validated this approach to be able to identify processes critical for blood-stage growth. Through this project we expect to identify dozens of genes critical for parasite virulence and development processes that are novel targets on which drug discovery projects can be initiated. An additional important outcome of our project will provide the malaria research community with a large collection of gene knockouts that will be a valuable resource for a multitude of other research projects.

Public Health Relevance

Malaria is a devastating global health problem and its elimination as an important disease requires new therapies. A major hurdle for development of new an anti-malarial drug is a lack of comprehensive information about the best targets. New drugs effective against multiple different targets in malaria parasites are essential to effectively eliminate malaria. Our project will provide this type of knowledge to identify new drug targets.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI094973-02
Application #
8225119
Study Section
Special Emphasis Panel (ZRG1-IDM-B (02))
Program Officer
Joy, Deirdre A
Project Start
2011-03-01
Project End
2016-02-29
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
2
Fiscal Year
2012
Total Cost
$330,750
Indirect Cost
$105,750
Name
University of South Florida
Department
Other Health Professions
Type
Schools of Public Health
DUNS #
069687242
City
Tampa
State
FL
Country
United States
Zip Code
33612
Campbell, Christopher O; Santiago, Daniel N; Guida, Wayne C et al. (2014) In silico characterization of an atypical MAPK phosphatase of Plasmodium falciparum as a suitable target for drug discovery. Chem Biol Drug Des 84:158-68
Balu, Bharath; Campbell, Christopher; Sedillo, Jennifer et al. (2013) Atypical mitogen-activated protein kinase phosphatase implicated in regulating transition from pre-S-Phase asexual intraerythrocytic development of Plasmodium falciparum. Eukaryot Cell 12:1171-8
Balu, Bharath; Maher, Steven P; Pance, Alena et al. (2011) CCR4-associated factor 1 coordinates the expression of Plasmodium falciparum egress and invasion proteins. Eukaryot Cell 10:1257-63