DC 9 - Linking mitochondrial to lipid metabolism in infections

• Objectives:

The aim of this project: investigate how mitochondrial metabolism is linked to central carbon and fatty acid metabolism and how altered substrate utilization, such as amino acid utilization, influences host-pathogen interactions. Specifically, we aim to understand how these metabolic changes affect lipid metabolism, plasma membrane events such as phagocytosis, and macrophage immune responses.

1. characterize how altered substrate utilization induced by small molecule inhibitors or CRISPR/Cas9 targeting affects mitochondrial metabolism in macrophages.
2. determine how tissue-specific amino acid metabolism affects lipid metabolism and function in macrophages;
3. characterize how fatty acid oxidation is influenced by altered substrate availability;
4. determine how altered mitochondrial metabolism affects immune cell function by focusing on plasma membrane events.

• Expected Results:

Macrophages undergo profound metabolic reprogramming during immune activation, and the dynamic regulation of metabolites is a key determinant of their function. The plasma membrane is an interface for host–pathogen interactions, where lipid composition regulates immune receptor function, signaling, and microbial entry. This project investigates how mitochondrial metabolism shapes these membrane-associated immune processes in macrophages. Using mass-spectrometry and isotope tracing approaches, we will study how mitochondrial substrate utilization, particularly of amino acids such as alanine and branched-chain amino acids, supports mitochondrial and fatty acid metabolism and influences lipid composition. Mitochondrial dysfunction can alter lipid diversity with direct consequences for plasma membrane dynamics and immune function. We will analyze how changes in mitochondrial substrate utilization affect lipid-dependent processes such as phagocytosis and host–pathogen interactions during viral and bacterial infections.

• Planned secondments:

Rafael Arguello lab (CIML, Marseille, France)
• perform functional metabolic profiling of immune cells with altered substrates using the SCENITH platform

Thomas Weichhart lab (MUW, Vienna, Austria)
• training to improve immunometabolic readouts for clinical use