School of Medicine and Health Sciences Poster Presentations

Title

Metabolomic Profiling of Serum Samples in Malaria: A Comparison of Naïve versus Immunized Mice

Document Type

Poster

Abstract Category

Immunology/Infectious Diseases

Keywords

malaria, metabolomics, data analysis, basic sciences, infectious diseases

Publication Date

Spring 5-1-2019

Abstract

Malaria is a life-threatening parasitic infection caused by Plasmodium species and transmitted by Anopheles mosquitoes through blood meals during which they deposit the parasites in the skin of the mammalian hosts. However, there are still remaining gaps in our understanding of the relationship between Plasmodium and its host, especially during the clinically silent stage before the onset of symptoms when the parasite replicates in the liver. Metabolomics is the study of chemicals in biosystems and is a very powerful tool that can investigate metabolism in-depth as well as its byproducts and associated networks. It can therefore help us gain a better understanding of the pathogenesis of malaria, and ultimately identify biomarkers of immunity that can be useful in furthering malaria drug and vaccine research. The goal of this project is to identify metabolites that are differentially expressed in the serum of mice immunized with radiation attenuated sporozoites that confers sterile immunity versus that of naïve mice. The serum samples were all collected during the parasite liver stage that lasts up to 48 hours after the mosquito's blood meal in our mice model. This was achieved by (1) preparation of serum samples collected from immunized and naïve mice 20 and 40 hours after the mosquito's blood meal for liquid chromatography and mass spectrometry, (2) untargeted metabolomic analysis and putative metabolite identification using Compound Discoverer, and (3) statistical analysis using MetaboAnalyst to determine significantly differentiated metabolites. A total of 1831 features were extracted from the samples, and of those 362 distinct differential features between the 4 groups were selected after principal component analysis, partial least square discriminant analysis, and hierarchical clustering. Of those, 21 and 28 putatively identified metabolites using the advanced mass spectral database mzCloud were found to be significantly different between the 2 groups at 20 and 40 hours after challenge respectively. KEGG analysis showed that those metabolites are involved in multiple pathways, including purine metabolism, the TCA cycle, and primary bile acid biosynthesis. Research is still ongoing, with the goal of validating our findings using targeted metabolomics and understanding the role of these differentiated metabolites in the development of malaria.

Open Access

1

Comments

Presented at Research Days 2019.

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Metabolomic Profiling of Serum Samples in Malaria: A Comparison of Naïve versus Immunized Mice

Malaria is a life-threatening parasitic infection caused by Plasmodium species and transmitted by Anopheles mosquitoes through blood meals during which they deposit the parasites in the skin of the mammalian hosts. However, there are still remaining gaps in our understanding of the relationship between Plasmodium and its host, especially during the clinically silent stage before the onset of symptoms when the parasite replicates in the liver. Metabolomics is the study of chemicals in biosystems and is a very powerful tool that can investigate metabolism in-depth as well as its byproducts and associated networks. It can therefore help us gain a better understanding of the pathogenesis of malaria, and ultimately identify biomarkers of immunity that can be useful in furthering malaria drug and vaccine research. The goal of this project is to identify metabolites that are differentially expressed in the serum of mice immunized with radiation attenuated sporozoites that confers sterile immunity versus that of naïve mice. The serum samples were all collected during the parasite liver stage that lasts up to 48 hours after the mosquito's blood meal in our mice model. This was achieved by (1) preparation of serum samples collected from immunized and naïve mice 20 and 40 hours after the mosquito's blood meal for liquid chromatography and mass spectrometry, (2) untargeted metabolomic analysis and putative metabolite identification using Compound Discoverer, and (3) statistical analysis using MetaboAnalyst to determine significantly differentiated metabolites. A total of 1831 features were extracted from the samples, and of those 362 distinct differential features between the 4 groups were selected after principal component analysis, partial least square discriminant analysis, and hierarchical clustering. Of those, 21 and 28 putatively identified metabolites using the advanced mass spectral database mzCloud were found to be significantly different between the 2 groups at 20 and 40 hours after challenge respectively. KEGG analysis showed that those metabolites are involved in multiple pathways, including purine metabolism, the TCA cycle, and primary bile acid biosynthesis. Research is still ongoing, with the goal of validating our findings using targeted metabolomics and understanding the role of these differentiated metabolites in the development of malaria.