Shuzhen sim    

I am a graduate student from Singapore, and my work focuses on the Aedes aegypti cell line immune responses to dengue virus. I am interested in host-pathogen interactions such as virus mediated
immune suppression, and am exploring these mechanisms in mosquito cells. VIDEO PRESENTATION / Contact: ssim@jhsph.edu

Bio - current research - cv - links

Bio:

I am a graduate student from Singapore, and my work focuses on the Aedes aegypti cell line immune responses to dengue virus. I am interested in host-pathogen interactions such as virus mediated immune suppression, and would like to explore these mechanisms in both insect and vertebrate cells.


Current research:
Use of cell line system
We have established an Ae. aegypti cell line system to further dissect mosquito immune responses to dengue virus (DENV). The use of the Aag2 cell line avoids the structural complexity of whole mosquitoes, provides a more sensitive method of detecting changes in gene regulation, and is easier to scale up for semi-high throughput assays such as RNAi screens.

Immune suppressive activity of DENV in the cell line
In order to study the effect of DENV infection on insect cell immune gene expression, a microarray analysis was carried out on live and heat-inactivated (HI) DENV infected Aag2 cells.

Fig 1: Live DENV up-regulates half as many immune genes as heat inactivated (HI) DENV, while down-regulating twice as many immune genes. Significantly regulated genes are shown here arranged by functional class; immune genes are shown in red.










Fig 2: Many immune genes are oppositely regulated in live DENV-infected cells and Cactus-silenced (Rel1 activated) mosquitoes. Cactus silencing simulates Toll pathway activation and results in the production of numerous anti-microbial effector molecules. Immune genes regulated by live DENV in the Aag2 cell line and by Cactus silencing in whole mosquitoes were clustered. Green indicates downregulation; red indicates upregulation.

Future directions

We are currently studying this immune suppression in more detail to determine which immune pathways the virus is acting on, and are particularly interested to determine if known mechanisms of DENV immune suppression in mammalian cells are also at work in invertebrate cells.


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