In recent years, Nathalie Pujol and Jonathan Ewbank have chosen to focus on how the epidermis of C. elegans reacts to infection by natural fungal pathogens. Its response encompasses a pathogen-specific reaction and a more generic stress response. Together these help C. elegans fight infection.
An important part of the reaction of the epidermis to infection is a rapid induction of the expression of many antimicrobial peptide genes. We are dissecting the molecular mechanisms that control this innate immune response, and have started to delineate the different signalling pathways that control it. In parallel, Nathalie Pujol initiated a new research direction, using cell biology as a way to understand the intimate relationship between innate immune responses and tissue repair.
The intricate microtubule (green) and actin (red) cytoskeleton in the epidermis of C. elegans.
Copyright Sébastien Mailfert and Nathalie Pujol, CIML
In the coming years, we aim to extend these studies and provide an integrated view of innate immune mechanisms in C. elegans by taking a number of complementary approaches:
- To identify all the genes that intervene in the response of C. elegans to fungal infection, and find novel signalling components, we use a combination of direct genetic screens and genome-wide RNAi screens.
- We use in vivo TAP-tag, co-IP and ChIP approaches, together with Y1H and Y2H screens, to characterise protein complexes involved in signalling networks.
- We apply classical immunofluorescence and cryo-immuno EM methods, in combination with advanced quantitative in vivo microscopy and modelling to gain insight into innate immune signalling at the sub-cellular level.
- To relate these elements to the physiology of the whole organism, we study the organismal response to infection, in order to construct a complete model of how C. elegans fights infection.