Professor Rothman discovered key molecular machinery responsible for transfer of materials among compartments within cells, providing the conceptual framework for understanding such diverse and important processes as the release of insulin into the blood, communication between nerve cells in the brain, and the entry of viruses to infect cells. Numerous kinds of tiny membrane-enveloped vesicles ferry packets of enclosed cargo. Each type of vesicle must deliver its specialized cargo to the correct destination among the maze of distinct compartments that populate the cytoplasm of a complex animal cell. The delivery process, termed membrane fusion, is fundamental for physiology and medicine, as pathology in this process can cause metabolic, neuropsychiatric and other diseases. Rothman reconstituted vesicle budding and fusion in a cell-free system (1984) and discovered the complex of SNARE proteins (1993) which mediates membrane fusion and affords it specificity. He also uncovered the GTPase-switch mechanism which controls coated vesicle budding in the cell (1991).

Rothman has also contributed to other fields. Together with Gero Miesenbock, he showed how patterns of synaptic activity in neural networks could be recorded optically using encoded synapto-pHlourins (1998). He discovered that hsp70’s are ATPases (1986) and peptide binding proteins (1989), thereby revealing how these molecular chaperones cycle on and off proteins to control their folding/unfolding. On theoretical grounds, he proposed (1981) that the role of the Golgi is to iteratively purify proteins, using its cisternae like plates in a distillation tower, an idea now implicit in all models of Golgi dynamics; and he provided the first evidence of sequential processing and vectorial transport across the stack (1981-1985). Rothman’s current research concerns the biophysics of membrane fusion and its regulation in exocytosis; the dynamics of the Golgi apparatus at super-resolution; and the use of bio-inspired design in nanotechnology.