Biography
We study the regulatory mechanisms of host and intracellular pathogen interaction during infection.
Research
A major response of cells during pathogen infection is changes in gene expression, leading to changes in the proteins being produced in the cell. Proteins are essential biopolymers in all living organisms, playing roles as structural components of cells, enzymes, and immune response agents such as antibodies.
Regulation of gene expression can occur at two levels: transcription (where mRNA is synthesised in the cell nucleus by the macromolecular machine RNA polymerase) and translation (where mRNA is decoded into proteins in the cell cytoplasm by the macromolecular machine known as the ribosome).
When cells are stressed, specific gene expression pathways are activated (e.g. cytokines as part of the innate immune system). However, so far, very few studies have systematically studied these changes in gene expression at the level of translation. The primary reason is due to technical difficulties with global monitoring of protein synthesis. Transcriptional regulation has been previously studied; however there is evidence that a significant amount of regulation also occurs at the translational level. This makes sense as direct modulation of protein synthesis provides a faster and more efficient response to pathogen infection, as it circumvents de novo mRNA transcription, processing and transport to the cell cytoplasm. Translational control is a highly dynamic process and global studies have only recently become possible with the advent of RiboSeq - a high-throughput technique that allows capturing the location and abundance of all ribosomes on mRNAs, allowing precise global measurement of real-time protein synthesis.
We aim towards understanding the complex interplay of host and pathogen gene regulation, and its ultimate effect on their proteome and response to biotic stress.
Key Projects, Countries and Partners
(1) Intracellular pathogen and host interactions. Understanding the dynamics, molecular mechanisms, and host innate immunity relevance of translational control during intracellular bacteria, virus and Toxoplasma infections.
(2) Programmed ribosomal frameshifting in RNA viruses.
(3) Molecular mechanisms of eukaryotic RNA ThermoSwitches and their applications.
