Viral Codon Usage: A Novel Readout of Virus Evolution and Host Interaction

This PhD project will investigate the molecular mechanisms underlying host-specific responses to arboviruses, a group of pathogens that pose significant global health risks. Arboviruses such as dengue, zika, and chikungunya (CHIKV) affect more than 80% of the world’s population living in areas at risk. These viruses replicate efficiently in both vertebrate hosts and mosquito vectors, but with strikingly different outcomes: they cause severe disease in humans while remaining non-pathogenic in mosquitoes. Understanding the molecular basis of this contrast is critical for advancing our knowledge of arbovirus biology and identifying new strategies to disrupt transmission.

Focusing on CHIKV as a model system, the doctoral candidate will carry out a comparative analysis of host–virus interactions in human and mosquito cells. The project will begin with transcriptomic and translatomic profiling during CHIKV infection to map how gene expression and translation are altered in each host. By comparing these responses, the candidate will identify conserved pathways shared across species as well as host-specific mechanisms that distinguish pathogenic from non-pathogenic outcomes. This comparative framework will highlight molecular features that make vertebrate hosts susceptible to disease, while uncovering protective responses in mosquitoes that enable viral tolerance.

The expected outcome of the project is a detailed comparative map of CHIKV-induced changes in gene expression, alternative splicing, and translation across human and mosquito cells. This resource will reveal both conserved and unique pathways influenced by infection, clarifying why CHIKV produces pathogenic effects in humans but not in mosquitoes. Insights gained from this work could inform species-specific interventions aimed at disrupting viral transmission, ultimately contributing to the development of novel approaches to control arbovirus spread.

We are seeking a motivated candidate with a background in bioinformatics, virology, molecular biology, or related fields. Strong analytical and computational skills will be highly valued, along with experience in transcriptomic data analysis or an interest in applying statistical and modelling approaches to infection biology. Curiosity, adaptability, and enthusiasm for interdisciplinary research will be key for success.

The project will be complemented by several international secondments that broaden training and perspectives. In year 2, a two-month placement at GIMM (Morais) will provide advanced training in software and statistical methods for transcriptomic analysis. In year 3, a one-month stay at CNRS (Walczak) will focus on building computational models from the candidate’s data. Also in year 3, a one-week secondment at UCD (Teeling) will introduce the candidate to bat immune biology and bats’ exceptional viral responses, providing comparative insights into host tolerance.