Watschinger Lab

ETHER LIPID METABOLISM RESEARCH GROUP:
THE WATSCHINGER LAB

Our body synthesises a fascinating variety of lipids in order to maintain vital functions. Still, many processes and whole lipid classes are not well understood. Ether lipids including the plasmalogens form such a class of lipids. They are important for physiological processes like fine-structuring of the brain, protection of the eye from cataract, sperm maturation, and signalling. Altered ether lipid metabolism has been associated with an increasing number of disorders, including Alzheimer’s disease, Parkinson’s disease, chronic obstructive pulmonary disease, and COVID-19. However, the molecular mechanisms underlying these associations remain poorly understood.

The mission and fascination of my laboratory lies in unravelling the underlying molecular mechanisms in ether lipid metabolism to increase our understanding of the processes that can ultimately lead to disease in humans, thus providing novel treatment targets in the future. Our main focus lies on two enzymes in ether lipids metabolism, AGMO and PEDS1, whose genes we could describe during the last years.

Specifically, our group addresses the following research questions:

1. How are ether lipids synthesized and degraded? Our group investigates the molecular mechanisms controlling ether lipid metabolism, with particular emphasis on the enzymes PEDS1, which catalyzes the final step in plasmalogen synthesis, and AGMO, the only known enzyme that degrades ether lipids. Understanding how these enzymes function and are regulated is a central focus of our laboratory.

2. What are the physiological functions of plasmalogens? Although plasmalogens are abundant in the brain, heart, immune system, and reproductive tissues, many of their biological roles remain unclear. Our lab seeks to determine how these lipids influence membrane organization, cellular signaling, oxidative stress responses, and tissue-specific physiology.

3. How does altered ether lipid metabolism contribute to disease? We study how disruptions in ether lipid pathways are linked to disorders such as neurodevelopmental disorders and inherited plasmalogen-deficiency syndromes. A key objective is to identify the molecular mechanisms that connect lipid metabolism to disease pathology.

4. How do genetic variants affect ether lipid enzymes? By combining biochemical assays with model systems, we investigate disease-associated variants of AGMO and PEDS1 to establish genotype–phenotype relationships and understand how mutations alter enzyme activity and contribute to human disease.

To address these questions, we combine lipid biochemistry, enzymology, genetics, cell biology, and analytical lipidomics, while also developing new experimental tools for measuring ether lipid metabolism. Overall, our research aims to bridge fundamental lipid biochemistry with translational insights into metabolic and neurodegenerative diseases.

Publications

https://pubmed.ncbi.nlm.nih.gov/?cmd=search&term=Watschinger+K[AU]+NOT+Boner+AL&sort=date