After establishing his academic career in the United States (University of California, Los Angeles, Johns Hopkins University School of Medicine), in 1986 he returned to the Biozentrum as professor of structural biology.

He was co-founder of the Maurice E. Müller Institute for Structural Biology and its director from 1986 until reaching emeritus status in 2011.

[2][3] Aebi is recognized as a pioneer in integrative structural biology as well as mechano- and nanobiology.

[4][5] His work focused on the elucidation of the structure, function and assembly of the cyto- and nucleoskeleton and the nuclear pore complex (NPC), as well as the amyloid fibrils that are a hallmark of Alzheimer's disease.

[6] He studied the architecture of diverse supramolecular assemblies using a combination of light, electron and atomic force microscopy, X-ray crystallography, and protein engineering.