Deciphering cellular responses to pathogens using genomics data
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[S.l. : s.n.]
Radboud Universiteit Nijmegen, 30 november 2012
Promotor : Huynen, M.A.
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SubjectNCMLS 4: Energy and redox metabolism IGMD 8: Mitochondrial medicine
The respiratory tract is exposed to viral and bacterial infections that cause morbidity and mortality particularly in children, the elderly and immune-compromised individuals. Despite the importance of such infections, the mechanisms underpinning disease pathogenesis in the host are unclear. Generally, signals in biological systems are transmitted when proteins interact with each other. It is therefore imperative to investigate infection-induced regulation and expression of these moieties. Herein, we examined genomics and proteomics data generated from host-cells in response to infectious agents like the Respiratory Syncytial Virus. Using 2-D gel electrophoresis and bioinformatics; we uncovered apoptosis as an important process in alveolar epithelial cells after infection with various respiratory tract viruses. (Chapter 2) Proteins that are encoded from genes associated with genetic or infectious diseases have protein- and interaction-enrichment biases in general protein-protein interaction networks. We developed a method called Physical Interaction Enrichment to alleviate this issue. (Chapter 3) Invading pathogens compete directly or indirectly with their host-cells for iron. We developed a method called Iron Squelch to investigate gene response to infection with respect to the response of the same genes during iron-overload or iron-depletion. We found an iron-depletion profile for intracellular infections. (Chapter 4) Dendritic cells (DCs) are professional antigen presenters whose differentiation from monocytes following infection is unclear. MicroRNAs could be involved. We identified microRNAs that are over-expressed in DCs relative to their precursors; uncovered their target genes and characterize transcription factor binding sites in their promoters. (Chapter 5) Neutrophils are immune cells that can subdue bacterial infections. We examined LPS-induced gene expression changes in neutrophils extracted from whole blood of human volunteers. We uncovered interesting temporal response patterns. (Chapter 6) Further insights of events at the interface between host and pathogens shall improve as wet-lab and dry-lab researchers continue to cooperate. (Chapter 7)
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