Previously, Nathalie Pujol and Jonathan Ewbank focused on how the epidermis of C. elegans reacts to infection by natural fungal pathogens. They found that there is a pathogen-specific reaction and a response to damage that together help C. elegans fight infection. Going forward, and with Jonathan on secondment to ERINHA, Nathalie is now leading research to study how the skin senses damage and exploring the potential contribution made by mechanical coupling between the extracellular matrix and the epidermis. The vibrant transdisciplinary CENTURI community on the Luminy campus provides an ideal collaborative environment for this innovative research.
An important part of the reaction of the epidermis to infection is a rapid induction of the expression of many antimicrobial peptide genes. Having dissected the molecular mechanisms that control this innate immune response, and delineated the different signalling pathways that control it. Nathalie Pujol recently initiated a new research direction, using cell biology as a way to understand the intimate relationship between innate immune responses and tissue repair. Microtubule plus-end dynamics link wound repair to the innate immune response | eLife (elifesciences.org)
The intricate microtubule (green) and actin (red) cytoskeleton in the epidermis of C. elegans.
Copyright Sébastien Mailfert and Nathalie Pujol, CIML
Epithelia are in constant interaction with adjacent extracellular matrices (ECMs), which are a source of biochemical signals and provide mechanical support. While the role of basal ECMs in relaying mechanical information to influence cell migration or fate has been well described, less is known about apical ECMs (aECMs) in animals. In C. elegans, mechanical coupling of the aECM to the epidermis is important during elongation in embryos. We have shown that in adults, mutants with structural changes that soften the aECM activate an immune response similar to physical injury or infection (Meisosomes, folded membrane platforms, link the epidermis to the cuticle in C. elegans | bioRxiv ; Damage Sensor Associated with the Cuticle Coordinates Three Core Environmental Stress Responses in Caenorhabditis elegans | Genetics | Oxford Academic (oup.com)). To establish how changes in the aECM impact cytoskeleton dynamics and the immune response, in the coming years, we propose to:
(1) characterise the cellular structure(s) relaying aECM tension to the epidermis,
(2) define the biophysical properties of the skin and formulate a predictive model,
(3) identify and characterise the key components of the mechano-sensing and signalling pathway through forward and reverse genetics.
We therefore hope to obtain a complete picture of how these two skin layers function together to protect the animal from injury and infection, and establish an efficient surveillance mechanism controlling the innate immune response.