Synthesis and cell imaging of fluorescent plasmalogens

• Applicant: Dr. Caroline Knittel
• Subject Area: Biological and Biomimetic Chemistry ; Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2022 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 501394104

Plasmalogens are peroxisome-derived phospholipids containing a characteristic enol ether moiety at the sn-1 position of the glycerol backbone and are thought to play an important role as membrane structural elements and endogenous antioxidants. Despite their ubiquity and likely importance in humans, numerous questions about plasmalogen subcellular distribution, cell trafficking, and metabolism remain unanswered. Although plasmalogen deficiencies are often observed in devastating human diseases including cancer, Alzheimer’s, and Zellweger’s syndrome, there is a lack of selective methods for detecting plasmalogens as biomarkers. We intend to develop fluorescent probes for tracking plasmalogens. To label endogenous plasmalogens in livings cells we will develop probes that selectively react with the enol ether bond for fluorescence labeling and determine the subcellular localization of these essential phospholipids using live cell imaging techniques. In addition, we intend to bioorthogonally tag synthetic plasmalogens as well as metabolic plasmalogen precursors and explore plasmalogen cell trafficking after exogenously adding these labeled analogs to living cells. Considering the immense need of unraveling the impact that plasmalogens have on cellular biology, we believe that this first of its kind study will provide essential knowledge about the subcellular distribution of these lipids and serve as a foundation for the future elucidation of the role of plasmalogens in human disease.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Neal Devaraj