Organelles during aging and longevity
1 PhD project offered in the IPP summer call Molecular Mechanisms in Genome Stability & Gene Regulation
Scientific Background
Aging is characterized by the gradual decline of tissue function. However, age progression can be slowed by interventions such as diet. One key component of the diet are lipids, which serve as energy reservoirs, and are also essential to cellular homeostasis as they constitute the building blocks of membranes. In the context of aging, specific lipids are potent modulators of lifespan. For example, monounsaturated fatty acids correlate with human longevity and extend lifespan in C. elegans. However, despite their importance for cellular and organismal homeostasis it remains largely unknown how lipids drive cellular changes underlying aging and if those can be leveraged to promote longevity. Our overarching goal for is to understand how organelles involved in lipid homeostasis influence lifespan.
PhD Project: Identification of how lipid droplets impact tissue homeostasis during aging and longevity
The major lipid reservoirs in cells are lipid droplets. These conserved cellular organelles are key for lipid metabolism as they are specialized in storing and hydrolyzing and they are differentially regulated during aging and disease. We recently discovered the beneficial effect of lipid droplets for longevity especially in the context of monounsaturated fatty acids. However, which mechanism is supported by lipid droplets during longevity remains largely unclear. One exciting possibility is that lipid droplets are beneficial when they accumulate in lipid storage tissues by providing energy during the geriatric stages of life and by sequestering toxic lipids that could damage membranes. To understand how lipid droplets modulate longevity in vivo, the PhD student will use C. elegans lifespan studies in combination with tissue-specific manipulations (via RNAi), metabolomics mass spectrometry, and cell biology including fluorescence microscopy. The project builds on preexisting mutants and protocols to manipulate cellular lipid content as well as on lifespan assays that we are currently executing. The PhD student is expected to perform bioinformatic analysis of the gene expression and mass spectrometry data supported by IMB’s core facilities. Training on all aspects of the project will be provided to support the PhD student and no specific expertise is required other than a strong background in cell biology (molecular biology, biochemistry or related). A high motivation for fundamental biology and excellent teamworking skills are required.
If you are interested in this project, please select Papsdorf as your preference in the IPP application platform.
Publication relevant to this project
Papsdorf K, Miklas JW, Hosseini A, Cabruja M et al. (2023) Lipid droplets and peroxisomes are co-regulated to drive lifespan extensions in response to mono-unsaturated fatty acids. Nature Cell Biology, 25(5):672-684. doi: 10.1038/s41556-023-01136-6 Link
