Spatial and functional characterization of neuronal lipids in health and disease

• Applicant: Dr. Antonino Asaro
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Biochemistry ; Cell Biology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 455109571

Profoundly understanding the brain and its diseases will require a deep understanding of the biology of its cells. Single-cell multi-omics technologies are giving us an unprecedented view but with persisting limitations. There is a particular need to explore polarized cells such as neurons at subcellular resolution. Their major domains – soma and neurites – differ radically in morphology, signaling properties, cytoskeletal organization, and physiological functions. While much has been learned about neuronal RNAs and proteins and the functional importance of their subcellular localization, little is known about the composition and functions of neuronal lipids, due to their complexity and a lack of analytical tools. Lipids play central roles in the biology of neurons and have been implicated in a wide range of diseases. This project will broaden our understanding of their compartmentalization and functions in neurons. I will grow iPSC-derived neurons on microporous membranes and use mass-spectrometry based lipidomics to spatially profile the lipid composition of soma and neurites. Subsequently I will chemically modify specific lipids to control and trigger lipid-mediated signaling pathways. By studying soma and neurites through -omics analysis and biochemical investigations, I hope to shed new light on the roles that lipids play in pathways that are essential to both healthy brain functions and pathological processes.

• DFG Programme: WBP Fellowship
• International Connection: Switzerland
• Host: Professor Dr. Howard Riezman