The role of C. elegans fatty acid metabolism in pathogen defense

• Applicant: Dr. Katja Dierking
• Subject Area: Animal Physiology and Biochemistry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 552101931

When an organism is infected by a pathogen, its survival often depends on its capacity to modify its metabolism. This adjustment provides energy for cellular defenses, enhances defensive functions, such as fortifying cell membranes, or generates metabolites that signal for defense activation. Fatty acid (FA) metabolism is a significant pathway closely interconnected with the immune response. FAs are fundamental building blocks of membrane phospholipids and storage lipids and can function as signaling molecules. Deciphering the precise changes in host FA metabolism during bacterial infection presents a significant challenge. The nematode Caenorhabditis elegans is a highly suitable and convenient model for studying FA metabolism and its roles in pathogen defense. While previous studies have investigated the role of FA metabolism in the defense of C. elegans against various human pathogens, its role in defense against the natural insect and nematode pathogen Bacillus thuringiensis is unclear. Our previous work indicates that modulations in FA metabolism affect C. elegans survival against B. thuringiensis infection, but in a different way than previously reported for other pathogens. This may be due to the unique infection process of B. thuringiensis that involves spores, which are associated with pore-forming toxins. This project aims to further investigate how modulations in FA metabolism affect defense against B. thuringiensis infection in C. elegans. To this end, we plan to (1) identify the involved FAs, (2) clarify which aspects of FA metabolism (de novo synthesis, FA ß-oxidation, and/or membrane homeostasis) are involved in defense against B. thuringiensis, and (3) identify transcriptional regulators that link FA metabolism to pathogen defense. This project will allow us to identify the processes of FA metabolism that are involved in C. elegans resistance and/or tolerance to B. thruingiensis infection and pinpoint key regulators of the still only poorly understood mechanisms underlying metabolic immunity in the context of B. thuringiensis infection. As metabolic functions have often been conserved across evolution, the generated results may yield new general insights into metabolic mechanisms of defense against pore-forming toxins, which are produced by many pathogenic bacteria.

• DFG Programme: Research Grants