From: Anantharaman, Vivek (NIH/NLM/NCBI) [C]
Sent: Sunday, March 09, 2008 11:09 PM
To: NLM/NCBI List ncbi-seminar
Subject: CBB seminar, Tuesday 3/11/2008, 11 am, B2 Library

CBB Seminar 11:00 am Tue Mar 11, B2 Library


Aspects of Parasite and Host biology in Malaria.

Vivek Anantharaman

 

The apicomplexan Plasmodium causes malaria in humans and other vertebrates. The sporozites are transferred from mosquitoes in to humans, and one of the later stages in its lifecycle the merozite infects the host erythrocyte. Infected erythrocytes are sequestered in various human tissues or organs, such as the heart, liver and brain.  The rodent parasite P.berghei provides a good animal model for cerebral malaria caused by P.falciparum. This talk will discuss the genes and the corresponding predicted biochemical systems identified using a combination of microarray-based expression data and sequence analysis in studies on : 1) fever response in P.falciparum 2) host response in rodent cerebral malaria model.  

Febrile temperature response in P. falciparum

High-density oligonucleotide microarray analysis of differential expression levels of individual genes in asexual-stage Plasmodium falciparum parasite cultures incubated at 37°C and 41°C (an elevated temperature that is equivalent to malaria-induced febrile illness in the host) identified altered expression profiles in 336 of approximately 5,300 genes (6.3% of the genome) had altered expression profiles. In-depth sensitive sequence profile analysis revealed that febrile temperature-induced responses caused significant alterations in the major parasite biologic networks and pathways and that these changes are well coordinated and intricately linked. One of the most notable transcriptional changes occurs in genes encoding proteins containing the predicted Pexel motifs that are exported into the host cytoplasm or inserted into the host cell membrane and are likely to be associated with erythrocyte remodeling and parasite sequestration functions. Using our sensitive computational analysis, we were also able to assign biochemical or biological functional predictions for numerous previously uncharacterized genes.

 

Experimental Cerebral Malaria in a rodent model

By using the P.berghei ANKA murine model of experimental cerebral malaria (ECM) and high density oligonucleotide microarray analysis, 200 host molecules were identified (a majority previously not identified) with altered expression patterns in the brain that are strongly associated with the manifestation of ECM. Using sequence analysis these proteins were classified into eleven categories based on function and subcellular localization. In addition to several molecules of the immune system, these molecules were classified as anti-apoptotic factors, transcription factors, receptors, proteins involved in signal transduction and cell-cell interaction and molecules that appear to constitute a regenerative or tissue-repair response to the brain injury. Details of these molecules and the systems they participate in will be presented

 

 
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Vivek Anantharaman, PhD
National Center for Biotechnology Information,
National Library of Medicine,
National Institutes of Health,
Bldg. 38A,Rm. N507A, 8600 Rockville pike,
Bethesda, MD 20894, USA
Phone: (301)443-1194
Email: ananthar@mail.nih.gov