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Doris Höglinger 
Lipid signaling and lysosomal biology

Groupleader: Doris Höglinger

Our group is interested in unravelling the mechanisms behind lipid-mediated signalling events. Certain lipid species, especially ones belonging to the biologically active sphingolipids, are powerful signalling molecules involved in many central processes. Therefore, cells must exert tight control over signalling lipid levels. One control checkpoint is the lysosome; an organelle responsible for the breakdown of cellular material such as proteins, nucleic acid, carbohydrates and lipids.  Specifically, many sphingolipid degrading enzymes are localized in the lysosome and any malfunction in this catabolic cascade leads to devastating pathologies. As many mechanisms of lysosomal lipid homeostasis are still unknown, we are interested in studying the lysosome in general and its role in lipid-mediated signalling in particular.

For example, we are pursuing the following questions:

I. What are the protein effectors of signalling lipids?

We have recently developed novel chemical biology tools which allow the identification of protein interactors of single lipid species and plan to further develop this technology. Applied to disease-relevant lipids such as sphingosine, we hope to gain insight into the mechanisms of lipid-mediated signalling and potentially identify new avenues for treatment.

II. How is lipid transport organized?

It is still unclear how the removal or reuse of the breakdown products upon degradation of complex lipids by lysosomal catabolic enzymes is coordinated. By directly visualizing lipid transport from the lysosome, we aim to uncover the mechanisms responsible for establishing and maintaining routes for lysosomal lipid export.

To achieve these goals, we develop and employ novel chemical biology tools complemented with cell biology studies in mammalian cells. Using lysosomal storage diseases as models, we aim to uncover novel pathways and to advance the concept of the lysosome as a signalling hub.