Dissecting the host response underlying recognition of a diverse group of pathogens (360G-Wellcome-219448_Z_19_Z)

Multicellular organisms use systemic signals to transmit biological information across tissues in order to co-ordinate responses to stress or infection. Discovering such signals, how they spread and what responses they trigger is therefore of paramount importance for organismal development. We have previously introduced the first tractable animal system to investigate a diverse group of eukaryotic pathogens, the oomycetes, which cause deadly infections in humans, as well as the model organism Caenorhabditis elegans. We have now discovered that C. elegans is able to sense these pathogens in neurons and mount a protective transcriptional response, the hallmark of which is the induction of conserved chitinase-like proteins in its epidermis. We propose to use comprehensive molecular genetics, cell biology, biochemistry, metabolomics and developmental imaging to determine the host response underlying pathogen recognition and elucidate the molecular gene network underlying the mounting of this response via neuron-to-epidermis signal exchange. Studying intercellular signalling requires a system-wide approach and, to this end, C. elegans offers a great opportunity to investigate this fundamental problem at the whole organism level. The proposed work will expand our knowledge on core cell and developmental biology mechanisms of intercellular signal exchange and immune response in the context of oomycete recognition.