Finding Vaccine Candidates for Malaria
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Transcript of Finding Vaccine Candidates for Malaria
Finding Vaccine Candidates for MalariaA Bioinformatics Approach
Our Methods1. Find malarial proteins containing regulatory
domains
2. Investigate the other domains identified for these proteins
3. Check for predicted transmembrane regions
4. Check for annotated signal peptide
Allison WeisProfessor Dietlind GerloffDepartment of Bimolecular EngineeringSummer 2008
Continuing Worko Expression dataIs the protozoa expressing this protein while in the human red blood cell?
o Discover more signaling motifs
o Predict disulfide bridgesIndicates extracellular location
o Asses the rate of regulatory and transmembrane proteins in non-parasitic eukaryotes
o Assess accuracy of annotations and predictions for malaria
Background
A disease of the underprivilegedo 2.5 billion largely impoverished people are at risk for malaria
o More than 1 million people die of malaria a year
o 1 in every 5 child deaths in Africa is due to malaria
o Malaria is both worsened by and contributes to the poverty level of the communities it infects
Parasitic Lifecycle• Complex and multi-stage• Requires larges amounts of protein import and export
References:World Health Organization http://www.who.int/topics/malaria/en/Przyborski J. and Lanzer M. “The Malarial Secretome”. Nature. Vol 306. 10. December 2004.
Objective
o Regulatory proteins contain highly conserved genes that could be consistently recognized by the body’s immune system
Rationale
o Find good vaccine candidates among malaria proteins
Assumptionso The parasite is affecting the host cell through direct regulatory processes o Most regulatory domains are intracellular o To affect the human proteins, the parasitic proteins need to be exported or presented on the membrane surface
?FIKKs
Current Resultso 13 transmembrane, non-FIKK proteinso 1 signal peptide, non-FIKK protein
Protein Transmembrane
Kinase Signal Other
MAL8P1.42 1378
PF14_0320 1571
MAL7P1.127 1859
PFF1370w 340
PF11_0464 2146
PF11_0156 777
PFA0380w 1586
PF11_0521 3223
PFEMP
PFI0160w 3241
PFF1370w 3176
PF14_0264 2433
MAL8PI.23 8879
MAL8P1.113 5896
peptidase
PF11_0127 2451
immunoglobulin