Easha Vigneswaran

PhD thesis:

Deciphering the molecular mechanisms of Zika virus infection during pregnancy using 3D trophoblast organoid models.

Zika virus (ZIKV) is a mosquito-borne virus, most notable for its 2015/16 epidemic in the Americas, is considered most consequential during pregnancy due to vertical transmission to the developing foetus. Although the Asian/American lineage was initially considered more virulent due to its association with severe neurological defects, emerging evidence indicates that the African lineage is more neuropathogenic, often causing early foetal demise and spontaneous abortions. At present there is no licensed vaccine or antiviral used to treat ZIKV infection, therefore, it is crucial to elucidate the molecular mechanisms driving productive placental infection to mitigate the severe risks posed to the developing foetus. My research will employ a comparative virology approach to assess ZIKV placental infection dynamics using a 3D trophoblast organoid model, characterising the immune landscape and define molecular differences in how ZIKV lineages modulate the maternal - foetal interface to influence foetal neurodevelopment.

Who or what inspired you to pursue your research interests?

During my undergraduate placement in viral immunology and vaccine design, I developed an appreciation for translational biology and the necessity of basic science to drive therapeutic development. The experience also highlighted the limitations of traditional cell lines and animal models, motivating my interest in leveraging 3D organoid systems as physiologically relevant models for studying viral pathogenesis. Having completed my master's research on Zika virus, I wanted to continue studying this neglected tropical disease, which disproportionately affects vulnerable populations. As climate change expands the habitat of Aedes mosquito vectors, understanding maternal-foetal infection dynamics is essential for anticipating and preventing future ZIKV outbreaks.