Finding Vaccine Candidates for Malaria

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Finding Vaccine Candidates for Malaria A Bioinformatics Approach Our Methods 1. 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 Weis Professor Dietlind Gerloff Department of Bimolecular Engineering Summer 2008 Continuing Work o Expression data Is the protozoa expressing this protein while in the human red blood cell? o Discover more signaling motifs o Predict disulfide bridges Indicates 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 underprivileged o 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 Assumptions o 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 ? FIKK s Current Results o 13 transmembrane, non-FIKK proteins o 1 signal peptide, non-FIKK protein Prote in Transmembra ne Kina se Sign al 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 peptida se PF11_0127 2451 immunoglobu lin

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Current Results. Objective. Background A disease of the underprivileged 2.5 billion largely impoverished people are at risk for malaria More than 1 million people die of malaria a year 1 in every 5 child deaths in Africa is due to malaria Malaria is both worsened by - PowerPoint PPT Presentation

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Page 1: 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