PIN-ning down Host-Parasite interactions
Microscopy image
This image was taken on the Operetta CLS High Content Analysis System. It shows Tac12 infected cells.
In green : schizont
In orange : T. annulata parasites
© Angélique Amo / Audrey Chansard
We are interested in how infectious agents develop intricate mechanisms to hijack the genetic and epigenetic machinery of their host cells to change phenotypic states. We developed a research program to investigate how the intracellular parasite Theileria annulata hijacks host signaling pathways to maintain cell transformation. Theileria is the only parasite known to transform it’s host cells into tumor-like cells. We want to understand how it does this and how we can stop it.
We have identified signaling pathways and oncogenic events induced by parasite infection. Our integrated approach uses a combination of parasite genomics, drug modelling, and experimental validation.
- We showed that Theileria parasites transform host cells by hijacking the oncogenic signaling and epigenetic machinery, including the transcription factors (cJun and HIF1a), chromatin regulators (SMYD3) and microRNA networks
- We identified a secreted parasite oncoprotein that activates host signaling: TaPin1 is a homologue of the Peptidyl Prolyl Isomerase Pin1. TaPin1 controls host transcriptional programs impacting proliferation, metabolism and invasion
- We recently used dual RNA-Seq and ChIP-Seq analysis of infected cells to identify a novel parasite epigenetic mark (H3K18me1) and for the first time we linked histone methylation to Theileria differentiation
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