EPFL Doctorate Award - 2023 - Mark Hanson
A systematic CRISPR approach to understanding the role of Drosophila antimicrobial peptides in immunity in vivo
EPFL thesis n°8880
Thesis director: Prof. B. Lemaitre
For his outstanding contribution to the field of innate immunity. In particular, for the characterization of new antimicrobial peptides in Drosophila and his insights on how environmental microbes shape animal immune system during evolution.
Antimicrobial peptides (AMPs) are host-encoded antibiotics that fight infectious microbes. These effector peptides are observed in plants, animals and fungi. In vitro studies have suggested AMPs eliminate microbes in a generalist fashion, with many AMPs contributing in redundant ways to defence against infections. However, studies in Drosophila flies brought this model into question, as highly-important interactions between single AMP genes or gene families seemed to explain much of the fly defence against specific microbes.
Here, I systematically deleted genes encoding AMPs in Drosophila to study the role of each AMP in immune defence individually or collectively in vivo. I confirmed that AMPs could act in an additive or redundant ways, agreeing with the cocktail idea. However, I found some AMP-pathogen interactions were remarkably specific, with numerous examples (for example, different Diptericins are specific for different microbes, or the peptide Drosocin is specific for the bacterium Enterobacter cloacae). Contrary to initial hypotheses, my work showed that AMPs are not simple generalist peptides in in vivo contexts.
This finding has significant implications for understanding why individuals are susceptible to certain infections. Indeed, this work on Drosophila antimicrobial peptides likely has relevance across animals, given the conservation of innate immune mechanisms between fruit flies and mammals.