Thomas F. McCutchan, Ph.D.
Chief, Regulation of Growth and Development Section
Description of Research Program
Plasmodium rRNA genes are unique with regard to copy number, genomic arrangement, and developmental regulation of transcription. The most unusual feature of Plasmodium rRNA genes is the differential expression of different rRNAs at discrete stages of the life cycle. Investigation of this unique system has numerous ramifications for the understanding of this parasitic protozoa.
Scientists have used species-specific regions of rRNA to study population dynamics of the parasite in the mosquitoes of an endemic area. Phylogenetic analysis of the rRNA sequences has led to a new and different understanding of the taxonomy of the Plasmodium genus and, in particular, to the conclusion that the human pathogen, P. falciparum, is closely related to avian parasites and has not co-evolved with its host. Secondary structural analysis of the RNAs has indicated functional differences between developmentally specific ribosomes that involve an alteration of the GTPase site. Drug studies indicate that the different ribosomes can be selectively targeted with different antibiotics. This system presents a unique opportunity to investigate translational control in a eukaryotic organism.
The other central project has involved the development of auxotrophic lines of malaria parasites that require supplemental nutrients to grow either in culture or in their natural hosts. The development of auxotrophic lines of bacteria, each with varying requirements as supplements for growth, was an essential tool in defining biochemical pathways in bacterial systems. Along with a general understanding of biochemistry, they have contributed to the definition of new drug targets. More recently the use of nonreverting auxotrophic mutants of Salmonella has led to a new generation of live vaccines, some of which have been approved for use. The generation of auxotrophic mutants of malaria parasites potentially holds some of the same promise for parasitology that it held for bacteriology.
Editorial Boards
- Experimental Parasitology
Research Group Members
Jessica Kissinger, Jun Li, M. J. Rogers
Selected Publications
(View list in PubMed.)
Rathore D, McCutchan TF, Sullivan M, Kumar S. Antimalarial drugs: current status and new developments. Expert Opin Investig Drugs. 2005 Jul;14(7):871-83. Review.
Rathore D, Nagarkatti R, Jani D, Chattopadhyay R, de la Vega P, Kumar S, McCutchan TF. An immunologically cryptic epitope of Plasmodium falciparum circumsporozoite protein facilitates liver cell recognition and induces protective antibodies that block liver cell invasion. J Biol Chem. 2005 May 27;280(21):20524-9.
McCutchan TF, Grim KC, Li J, Weiss W, Rathore D, Sullivan M, Graczyk TK, Kumar S, Cranfield MR. Measuring the effects of an ever-changing environment on malaria control. Infect Immun. 2004 Apr;72(4):2248-53.
McCutchan TF, Rathore D, Li J. Compensatory evolution in the human malaria parasite Plasmodium ovale. Genetics. 2004 Jan;166(1):637-40.
Fang J, Zhou H, Rathore D, Sullivan M, Su XZ, McCutchan TF. Ambient glucose concentration and gene expression in Plasmodium falciparum. Mol Biochem Parasitol. 2004 Jan;133(1):125-9.
Fang J, Sullivan M, McCutchan TF. The effects of glucose concentration on the reciprocal regulation of rRNA promoters in Plasmodium falciparum. J Biol Chem. 2004 Jan 2;279(1):720-5.
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