Malaria is a leading cause of human death and illness, causing each year 400-600 million cases of clinical malaria and 2-3 million deaths. Traditional measures to control and cure malaria are becoming increasingly neffective, and there is an urgent need for the development of new drugs and vaccines. Genomic studies and other hi-tech advances have produced a wealth of information about malaria parasites, yet using this information for functional analysis of the Plasmodium genome is hindered by a limited capability to genetically manipulate malaria parasites. We are developing technology for high throughput whole-genome mutagenesis screening of malaria parasites, using an efficient transposon-based method for parasite transformation. We propose developing this system for large-scale transposon mutagenesis of Plasmodium falciparum with the long-term goal of enhancing our understanding the genetic basis of the biology the malaria parasite, and greatly accelerating efforts to develop new therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21AI070888-03
Application #
7545551
Study Section
Special Emphasis Panel (ZRG1-PTHE-K (01))
Program Officer
Rogers, Martin J
Project Start
2006-06-15
Project End
2009-05-31
Budget Start
2007-10-09
Budget End
2009-05-31
Support Year
3
Fiscal Year
2007
Total Cost
$105,246
Indirect Cost
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
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Fonager, Jannik; Franke-Fayard, Blandine M D; Adams, John H et al. (2011) Development of the piggyBac transposable system for Plasmodium berghei and its application for random mutagenesis in malaria parasites. BMC Genomics 12:155
Auliff, Alyson M; Adams, John H; O'Neil, Michael T et al. (2010) Defining the role of mutations in Plasmodium vivax dihydrofolate reductase-thymidylate synthase gene using an episomal Plasmodium falciparum transfection system. Antimicrob Agents Chemother 54:3927-32
Balu, Bharath; Singh, Naresh; Maher, Steven P et al. (2010) A genetic screen for attenuated growth identifies genes crucial for intraerythrocytic development of Plasmodium falciparum. PLoS One 5:e13282
Tamez, Pamela A; Bhattacharjee, Souvik; van Ooij, Christiaan et al. (2008) An erythrocyte vesicle protein exported by the malaria parasite promotes tubovesicular lipid import from the host cell surface. PLoS Pathog 4:e1000118
Bhattacharjee, Souvik; van Ooij, Christiaan; Balu, Bharath et al. (2008) Maurer's clefts of Plasmodium falciparum are secretory organelles that concentrate virulence protein reporters for delivery to the host erythrocyte. Blood 111:2418-26
Maher, Steven P; Balu, Bharath; Shoue, Doug A et al. (2008) A highly sensitive, PCR-based method for the detection of Plasmodium falciparum clones in microtiter plates. Malar J 7:222
van Ooij, Christiaan; Tamez, Pamela; Bhattacharjee, Souvik et al. (2008) The malaria secretome: from algorithms to essential function in blood stage infection. PLoS Pathog 4:e1000084