Research Projects

The Dengue virus (DENV) is a major public health problem worldwide, primarily endemic to tropical countries. Despite its compact genome and reliance on host cells for propagation, only a few host factors have been validated, and the gene expression changes shaping host-virus interaction remain unclear. This necessitates the development of new tools and approaches to gain mechanistic insights into the host response to viral infection. Dengue is the most common mosquito-borne viral disease globally, affecting around 3.6 billion people and disproportionately affecting the poorest. The WHO prioritizes dengue as a neglected tropical disease. To gain a holistic understanding of the genetic basis and mechanism of dengue infection in the human host, this project aims to perform genome-wide gain-of-function and loss-of-function screens using CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) technology. The CRISPRi method is more specific and has a lower risk of genotoxity. Transgenic cells expressing dCas9 proteins will be transfected with pooled sgRNA libraries, followed by challenge with DENV2 virus for positive selection. The candidate genes will be used for network analyses with previously identified host factors to identify biological pathways and factors crucial for virus multiplication. Comparative challenge assays with other DENV serotypes will be conducted. This study will provide new insights and mechanistic understanding of viral pathogenesis and host response, potentially identifying critical targets for developing new anti-DENV therapies for effective disease management.