Malaria is a major infectious disease. Conservative estimates predict that 2-300 million people are afflicted and over a million children die from the infection each year. Plasmodium falciparum causes the most virulent form of human malaria. A striking feature of P. falciparum is its infection of the mature erythrocyte. Despite the fact that this is a non-endocytic host cell, its signaling protein such as the heterotrimeric Gs and G protein coupled receptors (GPCRs) regulate infection of P. falciparum. The overall objective of this project is to develop a detailed understanding of the molecular and cellular mechanisms by which P. falciparum and malaria parasites induce signaling in erythrocytes. It is anticipated that study will lead to understanding how signaling via the erythrocyte heterotrimeric Gs protein confers susceptibility to malarial infection and pathology and thereby contribute to understanding the basic biology of the parasite as well as disease. Molecular, microbial genetic tools using transfection, functional genomics combined with high resolution imaging techniques, biochemical assays as well as expertise in hematology and host genetics, will be used to investigate mechanisms that lead to vacuole formation, modify basic membrane properties of the host erythrocyte and confer resistance against malaria. The information gathered in these studies may be important to understanding mechanisms that underlie development of therapeutic strategies against malarial infection and hemolytic disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL079397-02
Application #
7020724
Study Section
Special Emphasis Panel (ZRG1-ELB (01))
Program Officer
Qasba, Pankaj
Project Start
2005-02-21
Project End
2009-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
2
Fiscal Year
2006
Total Cost
$93,682
Indirect Cost
Name
Northwestern University at Chicago
Department
Pathology
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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