Triggers and signaling pathways of metabolic activation in adipose tissue macrophages

• Applicant: Jan Ackermann
• Subject Area: Anatomy and Physiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 555457115

Metabolically activated macrophages are a well characterized macrophage subset with a unique specialization in lipid metabolism. For decades, they are linked to obesity and the subsequent development of type 2 diabetes. Over the past years several cell culture models have been developed to study their properties. With the combination of modern gene editing and high-throughput screening technologies it is now possible to screen for the underlying signaling pathways and determinants of macrophage phenotypes in cell culture. The aim of the project ‘Triggers and signaling pathways of metabolic activation in adipose tissue macrophages’ is the identification of genes and regulatory networks that define metabolic activation in ATMs by performing a pooled CRISPR screen. Since metabolic activation is a key process in the development of metabolic syndrome with the resulting comorbidities, a deeper understanding of its pathophysiology may open up new approaches for the treatment or prevention of metabolic syndrome. The design of the proposed project will additionally contribute to the understanding of metabolism and inflammatory pathways in macrophages. We successfully established a cell culture system that allows for valid and reliable induction of metabolically activated macrophages with palmitate in murine primary BMDMs. In the process time for the Walter Benjamin Stipendium, several macrophage cell lines, which are already available in our laboratory, shall be treated with palmitate and screened regarding their similarity to metabolically activated macrophages in AT. In the laboratories of Susan Carpenter at the University of California, Santa Cruz, the most advantageous cell line shall be edited, so that it expresses Cas9 endonuclease in combination with a suitable reporter, e.g. Plin2. Finally, the CRISPR screen shall be performed in the laboratory of Michael Böttcher at the Martin-Luther-Universität Halle/Wittenberg, who has about 10 years experience with CRISPR screens. This will help to understand the complex coherences of innate immunity and metabolism. It will generate valuable insights into the pathophysiology of obesity induced type 2 diabetes.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professorin Dr. Susan Carpenter, Ph.D.