The overall goal of the proposal is to evaluate tandem mass spectrometry (MS/MS) as a tool for malaria pathogenesis studies. Specifically, we will identify alterations in plasma protein expression during pregnancy malaria that may contribute to maternal anemia using MS/MS. Pregnancy malaria is an enormous public health problem in tropical countries, and placental inflammation has been related to disease and death for both the mother and her child. Paradoxically, malaria induces inflammatory responses in primigravid women (who suffer disease) as well as multigravid women (who are resistant to disease). We hypothesize that primigravid but not multigravid women will demonstrate changes in the level in TNF-regulated proteins that influence hemopoiesis. We propose to apply new proteomics tools to study the plasma proteome of a small group of malaria-infected pregnant women with well-characterized clinical and immunological data. Proteomics studies are a nonbiased approach to discover global protein expression, and will identify previously unrecognized factors that may influence pregnancy outcome in malaria-infected women. To study expression profiles of TNF-regulated proteins, the following Specific Aims are proposed: 1. Quantify the relative abundance of plasma proteins in a limited number of samples from malaria-infected pregnant women with poor and normal pregnancy outcomes by quantitative mass spectrometry; 2. Validate changes in the expression of TNF-regulated proteins (identified in Specific Aim 1) using ELISA in the original subset of samples as well as a larger number of samples from malaria-exposed women. This project will identify changes in protein expression during pregnancy malaria that contribute to maternal anemia, will validate the use of MS/MS for malaria pathogenesis studies, and may be the basis for large-scale studies of plasma proteomes of other malaria syndromes. ? ?
| Simpson, David C; Kabyemela, Edward; Muehlenbachs, Atis et al. (2010) Plasma levels of apolipoprotein A1 in malaria-exposed primigravidae are associated with severe anemia. PLoS One 5:e8822 |
