Bioengineering and biophysics of viral hemorrhagic fever

Doctoral Thesis

Viral hemorrhagic fever (VHF) is a group of acute diseases caused by highly infectious viruses including Ebola, Lassa, Dengue viruses. Its high mortality rate poses high risk to public health, however, studies on VHF have been hampered due to the non-availability of proper models and incomplete knowledge on its mechanism. In order to fill this gap, this thesis presented new bioanalytical, lab-on-chip and single-cell assays to investigate changes in vascular biology and macrophage immunometabolism induced by VHF viruses. Firstly, an organ chip was developed to mimic the hemorrhagic shock syndrome caused by VHF viruses in vitro and test experimental drug candidates. In addition, acoustic force spectroscopy was applied to investigate the effect of Dengue on the cellular viscoelastic properties of endothelial cells at single-cell level. Then, metabolic profiling of endothelial cells and macrophages upon Ebola viral protein exposure was performed on bulk-level. Finally, the...Show moreViral hemorrhagic fever (VHF) is a group of acute diseases caused by highly infectious viruses including Ebola, Lassa, Dengue viruses. Its high mortality rate poses high risk to public health, however, studies on VHF have been hampered due to the non-availability of proper models and incomplete knowledge on its mechanism. In order to fill this gap, this thesis presented new bioanalytical, lab-on-chip and single-cell assays to investigate changes in vascular biology and macrophage immunometabolism induced by VHF viruses. Firstly, an organ chip was developed to mimic the hemorrhagic shock syndrome caused by VHF viruses in vitro and test experimental drug candidates. In addition, acoustic force spectroscopy was applied to investigate the effect of Dengue on the cellular viscoelastic properties of endothelial cells at single-cell level. Then, metabolic profiling of endothelial cells and macrophages upon Ebola viral protein exposure was performed on bulk-level. Finally, the immunometabolism of human macrophages upon polarization was investigated by live single-cell metabolomics, setting the stage for future host-pathogen studies at single-cell level. Overall, this thesis will facilitate the understanding of VHF viruses and the development of treatment strategies. More importantly, the technologies developed here expectedly open up opportunities to combat the viruses that threaten global society.
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Viral hemorrhagic fever

Vascular permeability

Macrophage polarization