Protein synthesis is a fundamental requirement for the development of an organism. Plasmodium species expresse developmentally distinct rRNAs which suggests that the central catalytic component of the ribosome is constantly changing during development. We would expect to see coordinate control of different ribosomes and stage specific protein. The control regions of messenger RNAs that are expressed differentially in different stages of the life cycle, like the circumsporozoite protein message, have revealed consistent differences that appear to correlate with changes in ribosomes. The effect of these changes are currently being investigated in vivo by gene replacement. During the course of our work on the control of developmental regulation we have shown that thermoregulation in the form of cold-induced up-regulation of the transcription of a single rDNA unit is a component of developmental transitions that occur during the transmission Plasmodium falciparum from human to the mosquito. A strong, cold-stimulated promoter may offer an inducible promoter for the first time to the Plasmodium system. With such a tool we could produce ribozymes and antisense messagers simply by temperarily lowering culture temperature. To this end we transfected P. falciparum with a chimeric plasmid containing an S2-promoter region in alignment with a fragment of the luciferase gene, and measured mRNA levels at 26?C, 37?C, and 40?C. We found that a full range of control is accessible within the temperature ranges at which P. falciparum is viable in culture.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000208-22
Application #
6668876
Study Section
(LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
22
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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