Fellows Seminar – Deciphering the innate immune response: lessons from drosophila genetics

By Nicolas Matt, 2018 Fellow

In metazoans (multicellular animal organisms), protection against microorganisms involves both passive and active lines of defence. In insects, the chitinous outer cuticle protects organisms from the external environment and represents a passive means of protection. Besides this physical armour, insects have innate immunity, something that is common to all metazoans and which represents the oldest evolutionary immune system. In vertebrates, innate immunity is coupled with an adaptive immune system.

Functionally in insects, innate immunity is based on the recognition of pathogen motifs such as peptidoglycan. This leads to activation of an immune response through (i) systemic or local synthesis of antimicrobial peptides (AMPs) and (ii) phagocytosis of invaders. The expression of genes encoding AMPs are under the control of nuclear factor kappa B (NF-κB) family. 

In humans, aberrant regulation of NF-κB pathways is strongly suspected in many cancers and chronic inflammatory diseases. Efforts have been made to develop drug molecules that interfere with NF-κB signalling in inflammatory diseases. However, deactivation of the entire NF-κB pathway can lead to numerous adverse effects. This points to the need to understand whether it is possible to uncouple the activation of anti- and pro-inflammatory genes to preferentially target only the latter. 

The fruit fly Drosophila has already proven to be a powerful tool to decipher human diseases related mainly to cancer and neurological disorders. Using Drosophila as a model, we have identified new molecules that represent the "missing link" in understanding the complexity and selectivity of NF-κB signalling during the innate immune response.

^{Image taken from: Drosophila: Small fly, BIG impact, a short educational film by the Manchester Fly Facility}

• More information on Nicolas Matt and his USIAS project: Exploration of the chromatin inflammatory code in Drosophila and in mammals.